Cogprints: No conditions. Results ordered -Date, Title. 2018-01-17T14:26:12ZEPrintshttp://cogprints.org/images/sitelogo.gifhttp://cogprints.org/2014-02-25T12:40:16Z2014-02-25T12:40:16Zhttp://cogprints.org/id/eprint/9135This item is in the repository with the URL: http://cogprints.org/id/eprint/91352014-02-25T12:40:16ZThe Association of Antidepressant Medication and Body Weight GainObjective: To review the literature and discover which antidepressants are responsible for weight gain and then to discuss the areas with lack of adequate knowledge. Method: An electronic search was conducted through Medline, Pubmed, Cochrane library, and ScienceDirect. Forty nine empirical researches were identified and reviewed. Results: Amitriptyline, clomipramine, and mirtazapine have been associated with more weight gain induction in clinical studies, but not in animal-based studies. All TCAs have been reported to cause weight gain except protriptyline. MAOIs have been associated with weight gain. In SSRI group, citalopram and ecitalopram induce weight, yet mixed results exist for paroxetine and fluoxetine. Researches unanimously reported weight loss effect for bupropion. Some studies suggest contributing factors in the relationship of antidepressants with body weight changes including age, gender, base-line weights and treatment duration. Various results of different treatment durations have been reported in some cases but there are not continuous time-dependent studies for the influences of antidepressants on body weight changes. Conclusion: More studies are required to discover underlying mechanisms and the time-dependent effects of antidepressants on body weight changes.Sara Ranjbarsr769@uowmail.edu.auNagesh Brahmavar PaiChao Deng2012-11-09T19:37:13Z2012-11-09T19:37:13Zhttp://cogprints.org/id/eprint/8143This item is in the repository with the URL: http://cogprints.org/id/eprint/81432012-11-09T19:37:13ZCocaine self-administration in the mouse: A low- cost, chronic catheter preparationIntravenous drug self-administration is the most valid animal model of human addiction because it allows volitional titration of the drug in the blood based on an individual’s motivational state together with the pharmacokinetic properties of the drug. Here we describe a reliable low-cost mouse self-administration catheter assembly and protocol that that can be used to assess a variety of drugs of abuse with a variety of protocols. We describe a method for intravenous catheter fabrication that allows for efficient and long-lasting intravenous drug delivery. The intravenous catheters remained intact and patent for several weeks allowing us to establish stable maintenance of cocaine acquisition. This was followed by a dose response study in the same mice. For collaborators interested in premade catheters for research please make a request at www.neuro-cloud.net/nature-precedings/pomerenze.M PomrenzeM BarattaB CadleD.C. Cooper2011-12-16T00:08:51Z2011-12-16T00:08:51Zhttp://cogprints.org/id/eprint/7747This item is in the repository with the URL: http://cogprints.org/id/eprint/77472011-12-16T00:08:51ZA neuroeconomic theory of rational addiction and
nonlinear time-perception.Neuroeconomic conditions for “rational addiction” (Becker and Murphy, 1988) have
been unknown. This paper derived the conditions for “rational addiction” by utilizing a
nonlinear time-perception theory of “hyperbolic” discounting, which is mathematically
equivalent to the q-exponential intertemporal choice model based on Tsallis' statistics. It
is shown that (i) Arrow-Pratt measure for temporal cognition corresponds to the degree
of irrationality (i.e., Prelec’s “decreasing impatience” parameter of temporal
discounting) and (ii) rationality in addicts is controlled by a nondimensionalization
parameter of the logarithmic time-perception function. Furthermore, the present theory
illustrates the possibility that addictive drugs increase impulsivity via dopaminergic
neuroadaptation without increasing irrationality. Future directions in the application of
the model to studies in neuroeconomics are discussed.Ph.D Taiki Takahashi2011-12-16T00:08:33Z2011-12-16T00:08:33Zhttp://cogprints.org/id/eprint/7748This item is in the repository with the URL: http://cogprints.org/id/eprint/77482011-12-16T00:08:33ZToward molecular neuroeconomics of obesity.Because obesity is a risk factor for many serious illnesses such as diabetes, better
understandings of obesity and eating disorders have been attracting attention in
neurobiology, psychiatry, and neuroeconomics. This paper presents future study
directions by unifying (i) economic theory of addiction and obesity (Becker and Murphy,
1988; Levy 2002; Dragone 2009), and (ii) recent empirical findings in neuroeconomics
and neurobiology of obesity and addiction. It is suggested that neurobiological
substrates such as adiponectin, dopamine (D2 receptors), endocannabinoids, ghrelin,
leptin, nesfatin-1, norepinephrine, orexin, oxytocin, serotonin, vasopressin, CCK,
GLP-1, MCH, PYY, and stress hormones (e.g., CRF) in the brain (e.g., OFC, VTA,
NAcc, and the hypothalamus) may determine parameters in the economic theory of
obesity. Also, the importance of introducing time-inconsistent and
gain/loss-asymmetrical temporal discounting (intertemporal choice) models based on
Tsallis’ statistics and incorporating time-perception parameters into the neuroeconomic
theory is emphasized. Future directions in the application of the theory to studies in
neuroeconomics and neuropsychiatry of obesity at the molecular level, which may help
medical/psychopharmacological treatments of obesity (e.g., with sibutramine), are
discussed.Taiki Takahashitaikitakahashi@gmail.com2011-12-16T00:58:01Z2011-12-16T00:58:01Zhttp://cogprints.org/id/eprint/7740This item is in the repository with the URL: http://cogprints.org/id/eprint/77402011-12-16T00:58:01ZEarly Diagnosis of Alzheimer's Disease by NIRF Spectroscopy
and Nuclear Medicine
Novel approaches to Early Diagnosis of Alzheimer's Disease by NIRF Spectroscopy and Nuclear Medicine are presented and related cognitive, as well as molecular and cellular, models are critically evaluated.
Prof.Dr. I.C. Baianuibaianu@illinois.edu2009-03-28T09:30:03Z2011-03-11T08:57:20Zhttp://cogprints.org/id/eprint/6399This item is in the repository with the URL: http://cogprints.org/id/eprint/63992009-03-28T09:30:03ZEvaluation of Buprenorphine in a Postoperative
Pain Model in RatsWe evaluated the commonly prescribed analgesic buprenorphine in a postoperative pain model in rats, assessing acute postoperative pain relief, rebound hyperalgesia, and the long-term effects of postoperative opioid treatment on subsequent opioid exposure. Rats received surgery (paw incision under isoflurane anesthesia), sham surgery (anesthesia only), or neither and were treated postoperatively with 1 of several doses of subcutaneous buprenorphine. Pain sensitivity to noxious and nonnoxious mechanical stimuli at the site of injury (primary pain) was assessed at 1, 4, 24, and 72 h after surgery. Pain sensitivity at a site distal to the injury (secondary pain) was assessed at 24 and 72 h after surgery. Rats were tested for their sensitivity to the analgesic and
locomotor effects of morphine 9 to 10 d after surgery. Buprenorphine at 0.05 mg/kg SC was determined to be the most effective; this dose induced isoalgesia during the acute postoperative period and the longest period of pain relief, and it did not induce longterm changes in opioid sensitivity in 2 functional measures of the opioid system. A lower dose of buprenorphine (0.01 mg/kg SC) did not meet the criterion for isoalgesia, and a higher dose (0.1 mg/kg SC) was less effective in pain relief at later recovery periods and induced a long-lasting opioid tolerance, indicating greater neural adaptations. These results support the use of 0.05 mg/kg SC buprenorphine as the upper dose limit for effective treatment of postoperative pain in rats and suggest that higher doses produce long-term effects on opioid sensitivity.Dr. Leslie I. Curtinlicurtin@buffalo.eduJulie A. Grakowskyjg96@buffalo.eduMauricio Suarezmsuarez@ria.buffalo.eduDr. Alexis C. Thompsonathompso@ria.buffalo.eduDr. Jean M. DiPirrodipirrjm@buffalostate.eduDr. Lisa B.E. Martinlbmartin@buffalo.eduDr. Mark B. Kristalkristal@buffalo.edu2009-03-28T09:32:38Z2011-03-11T08:57:20Zhttp://cogprints.org/id/eprint/6385This item is in the repository with the URL: http://cogprints.org/id/eprint/63852009-03-28T09:32:38ZIngestion of amniotic fluid enhances the facilitative effect of VTA morphine on the onset of maternal behavior in virgin ratsPrevious research has shown that injection of morphine into the ventral tegmental area(VTA) facilitates the onset of maternal behavior in virgin female rats, and injection of the opioid antagonist naltrexone into the VTA disrupts the onset of maternal behavior in parturient rats. Placentophagia – ingestion of placenta and amniotic fluid, usually at parturition – modifies central opioid processes. Ingestion of the active substance in placenta and amniotic fluid, Placental Opioid-Enhancing Factor (POEF), enhances the hypoalgesic effect of centrally administered morphine, and more specifically, enhances δ- and κ-opioid-receptor-
mediated hypoalgesia and attenuates μ-opioid-receptor-mediated hypoalgesia. POEF (in placenta or amniotic fluid) ingestion does not, by itself, produce hypoalgesia. In the
present study, we tested the hypothesis that ingestion of amniotic fluid enhances the facilitative effect of opioid activity (unilateral morphine injection) in the VTA on the rate of onset of maternal behavior. Virgin female Long-Evans rats were given one intra-VTA injection of morphine sulfate (0.0, 0.01, or 0.03 μg, in saline) and an orogastric infusion of 0.25 ml amniotic fluid or saline once each day of the first three days of the 10-day testing
period. Subjects were continuously exposed to foster pups that were replaced every 12 h; replacement of pups was followed by a 15-min observation period. Maternal behavior
latency was determined by the first of two consecutive tests wherein the subject displayed pup retrieval, pup licking in the nest, and crouching over all foster pups, during the 15-min observation. We confirmed the previous finding that the VTA injection, alone, of 0.03 μg morphine shortened the latency to show maternal behavior and that 0.0 μg and 0.01 μg morphine did not. Ingestion of amniotic fluid (and therefore POEF) facilitated the onset of
maternal behavior in rats receiving an intra-VTA microinjection of an otherwise subthreshold dose of morphine (0.01 μg).Anne Neumannaneumann@buffalo.eduRobert F. Hoeyrhoey@buffalo.eduLindsey B. Daiglerldaigler@buffalo.eduDr. Alexis C. Thompsonathompso@ria.buffalo.eduDr. Mark B. Kristalkristal@buffalo.edu2009-07-02T01:52:05Z2011-03-11T08:57:22Zhttp://cogprints.org/id/eprint/6550This item is in the repository with the URL: http://cogprints.org/id/eprint/65502009-07-02T01:52:05ZCrosstalk Between Brain-Derived Neurotrophic Factor And N-Methyl-D-Aspartate Receptor Signaling In NeuronsGlutamate is the major excitatory neurotransmitter in brain exerting prosurvival effect on neurons via N-methyl-D-aspartate receptor (NMDAR) signaling under physiological conditions. However in pathological circumstances such as ischemia, NMDARs might have proapoptotic excitotoxic activity. In contrast brain-derived neurotrophic factor (BDNF) signaling via TrkB receptors has been largely considered to promote neuronal differentiation, plasticity and survival during normal development, and protect neurons in pathophysiological conditions antagonizing the NMDAR-mediated excitotoxic cell death. In this review we summarize recent evidence for the existent crosstalk and positive feedback loops between the BDNF and NMDAR signaling and point out some of the important specific features of each signaling pathway.Danko GeorgievHideo TaniuraYuki KambeYukio Yoneda2008-02-10T03:27:41Z2011-03-11T08:57:03Zhttp://cogprints.org/id/eprint/5925This item is in the repository with the URL: http://cogprints.org/id/eprint/59252008-02-10T03:27:41ZElevated glycogen synthase kinase 3 activity in Fragile X mice: key metabolic regulator with evidence for treatment potential Significant advances have been made in understanding the underlying defects of and developing potential treatments for Fragile X Syndrome (FXS), the most common heritable mental retardation. It has been shown that neuronal mGluR5-mediated signaling is affected in FX animal models, with consequent alterations in activity-dependent protein translation and synaptic spine functionality. We demonstrate here that a central metabolic regulatory enzyme, glycogen synthase kinase 3 (GSK3) is present in a form indicating elevated activity in several regions of the FX mouse brain. Furthermore, we show that selective GSK3 inhibitors, as well as lithium, are able to revert mutant phenotypes of the FX mouse. Lithium, in particular, remained active with chronic dosing, although its effects were transient even when given from birth. The combination of mGluR5 antagonist and GSK3 inhibitors was not additive. Instead, it was discovered that mGluR5 signaling and GSK3 activation in the FX mouse are coordinately elevated, with inhibition of mGluR5 leading to inhibition of GSK3. These findings raise the possibility that GSK3 is a fundamental and central component of FXS pathology, with a substantial treatment potential. Dr. Robert P. Bauchwitzrpb3@columbia.edu2007-11-22T01:49:16Z2011-03-11T08:57:00Zhttp://cogprints.org/id/eprint/5832This item is in the repository with the URL: http://cogprints.org/id/eprint/58322007-11-22T01:49:16ZCyclooxygenase Inhibition Limits Blood-Brain Barrier Disruption following Intracerebral Injection of Tumor Necrosis Factor-alpha in the RatIncreased permeability of the blood-brain barrier (BBB) is important in neurological disorders. Neuroinflammation is associated with increased BBB breakdown and brain injury. Tumor necrosis factor-alpha (TNF-a) is involved in BBB injury and edema formation through a mechanism involving matrix metalloproteinase (MMP) upregulation. There is emerging evidence indicating that cyclooxygenase (COX) inhibition limits BBB disruption following ischemic stroke and bacterial meningitis, but the mechanisms involved are not known. We used intracerebral injection of TNF-a to study the effect of COX inhibition on TNF-a-induced BBB breakdown, MMP expression/activity and oxidative stress. BBB disruption was evaluated by the uptake of 14C-sucrose into the brain and by magnetic resonance imaging (MRI) utilizing Gd-DTPA as a paramagnetic contrast agent. Using selective inhibitors of each COX isoform, we found that COX-1 activity is more important than COX-2 in BBB opening. TNF-a induced a significant upregulation of gelatinase B (MMP-9), stromelysin-1 (MMP-3) and COX-2. In addition, TNF-a significantly depleted glutathione as compared to saline. Indomethacin (10 mg/kg; i.p.), an inhibitor of COX-1 and COX-2, reduced BBB damage at 24 h. Indomethacin significantly attenuated MMP-9 and MMP-3 expression and activation, and prevented the loss of endogenous radical scavenging capacity following intracerebral injection of TNF-a. Our results show for the first time that BBB disruption during neuroinflammation can be significantly reduced by administration of COX inhibitors. Modulation of COX in brain injury by COX inhibitors or agents modulating prostaglandin E2 formation/signaling may be useful in clinical settings associated with BBB disruption.Dr. Eduardo Candelario-Jalilecandelario-jalil@salud.unm.eduDr. Saeid TaheriDr. Yi YangDr. Rohit SoodDr. Mark GrosseteteEduardo EstradaDr. Bernd L. FiebichDr. Gary A. Rosenberg2007-10-15T11:31:04Z2011-03-11T08:56:58Zhttp://cogprints.org/id/eprint/5754This item is in the repository with the URL: http://cogprints.org/id/eprint/57542007-10-15T11:31:04ZLack of analgesic efficacy in female rats of
the commonly recommended oral dose of
buprenorphinePrevious work in our laboratory showed that the recommended oral dose of buprenorphine (0.5 mg/kg) was not as effective
as the standard therapeutic subcutaneous dose for postoperative analgesia in male Long-Evans (hooded) and Sprague-Dawley (albino) rats. The aim of the current study was to extend this analysis to female rats. We measured the pain threshold in adult female rats in diestrus or proestrus before and 30 and 60 min after oral buprenorphine (0.5 mg/kg,), the standard subcutaneous dose of buprenorphine (0.05 mg/kg), or vehicle only (1 ml/kg each orally and subcutaneously). Female rats showed an increased pain threshold (analgesia) after subcutaneous buprenorphine but no change in pain threshold after either oral buprenorphine or vehicle only. Estrous cycle stage (proestrus versus diestrus) did not affect the analgesic effects of buprenorphine, but rats in proestrus showed significantly lower pain thresholds (less tolerance to pain) than did those in diestrus. These results show that the oral dose of buprenorphine recommended for postoperative analgesic care does not induce significant analgesia in female rats and therefore is not as effective as the standard subcutaneous dose.Dr. Alexis C. ThompsonDr. Jean M. DiPirroMr. Ahmad R. SylvesterDr. Lisa B.E. MartinDr. Mark B. Kristalkristal@buffalo.edu2009-06-10T08:01:36Z2011-03-11T08:57:22Zhttp://cogprints.org/id/eprint/6538This item is in the repository with the URL: http://cogprints.org/id/eprint/65382009-06-10T08:01:36ZSuppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEPFragile X Syndrome is the most common form of inherited mental retardation worldwide. A Fragile X mouse model, fmr1, with a disruption in the X-linked Fmr1 gene, has three substantial deficits observed in several strains: (1) sensitivity to audiogenic seizures (AGS), (2) tendency to spend significantly more time in the center of an open field, and (3) enlarged testes. Alterations in metabotropic glutamate receptor group I signaling were previously identified in the fmr1 tm1Cgr mouse. In this study, we examined the effect of MPEP, an antagonist of the group I metabotropic glutamate receptor mGluR5, on audiogenic seizures and open field activity of fmr1 tm1Cgr mice. Genetic analysis revealed synergistic reactions between fmr1tm1Cgr and inbred AGS alleles. In addition, AGS sensitivity due to the fmr1 tm1Cgr allele was restricted during development. Examination of phenotypes combining mGluR5 inhibition and Fmr1 mutation indicated that absence of FMRP may affect mGluR5 signaling through indirect as well as direct pathways. All strains of fmr1 tm1Cgr mice tested (FVB/NJ, C57BL/6J, and an F1 hybrid of the two) had a more excitable AGS pathway than wild-type, and consequently required more MPEP to achieve seizure suppression. At high doses of mGluR5 antagonists, a Fragile X specific tolerance (loss of drug activity) was observed. The tolerance effect could be overcome by a further increase in drug dose. In open field tests, MPEP reduced fmr1 tm1Cgr center field behavior to one indistinguishable from wild-type. Therefore, mGluR5 antagonists were able to rescue two of the major phenotypes of the FX mouse. Modulation of mGluR5 signaling may allow amelioration of symptoms of Fragile X Syndrome. Dr. Robert Bauchwitzrpb3@columbia.edu2005-04-13Z2011-03-11T08:55:51Zhttp://cogprints.org/id/eprint/4093This item is in the repository with the URL: http://cogprints.org/id/eprint/40932005-04-13ZOptimal Agonist/Antagonist Combinations Maintain Receptor Response by Preventing Rapid beta1-Adrenergic Receptor DesensitizationDesensitization is a serious side effect of many drugs. It is also a fundamental problem for modeling drug-receptor interactions. This study was designed to test a receptor model and a method to optimize agonist/antagonist combinations calculated to prevent receptor desensitization, which has relevance for many important drugs, including the b1-adrenergic agonist drugs. Because desensitization is a serious side effect, the beta1-adrenergic agonist drugs are no longer the logical treatment for heart failure and have been replaced by antagonist drugs represented by metoprolol (Lopressor). Although the scientific rationale for this remains unclear and because the agonist and antagonist drugs may be administered together in some medical circumstances, it is important to understand the early interactions of beta-agonist drugs with the beta-antagonist drugs at the level of the initial receptor response. Isoproterenol (Iso) or dobutamine (Dob) were given as intravenous solutions to rats with or without the beta1-antagonist, metoprolol (Met), which was given either as a fixed amount or as part of an agonist/antagonist combination. The Iso and Dob solutions alone demonstrated rapid desensitizaton, whereas the optimal Iso/Met and Dob/Met agonist/antagonist combinations significantly prevented desensitization while maintaining near maximal responses in all of the animals tested. The theory behind the model predicted these responses and fit the experimental data with reasonable biophysical parameters. This study supports the concept that the earliest events of receptor desensitization can be modeled and controlled at the level of the initial receptor response and also suggests that the beneficial effects of metoprolol for heart failure may result from its action on the earliest events of receptor activation. Richard Lanzara2005-03-16Z2011-03-11T08:55:49Zhttp://cogprints.org/id/eprint/4034This item is in the repository with the URL: http://cogprints.org/id/eprint/40342005-03-16ZA Psychedelic Neurochemistry of TimeAn accumulating literature suggests that a wide array of psychedelics can induce potent changes in time perception.Very little is known about the nature of these changes. However, the repeated theme of temporal distortion amongst many archives of psychedelic experiences strongly supports the notion that psychedelic drugs do, in some way, impact the underlying neurochemistry of time perception. This brief paper discusses examples of how psychedelics can change time perception and offers suggestions for further research.Dr. Kim A. Dawson2007-10-15T11:30:46Z2011-03-11T08:56:58Zhttp://cogprints.org/id/eprint/5755This item is in the repository with the URL: http://cogprints.org/id/eprint/57552007-10-15T11:30:46ZAnalgesic efficacy of orally administered
buprenorphine in rats: methodologic
considerationsBuprenorphine has been widely recommended for treatment of pain in rodents. We have previously documented that the recommended postoperative oral dose of buprenorphine in male Long-Evans rats, 0.5 mg/kg, is not as effective as the recommended parenteral dose of buprenorphine (0.05 mg/kg, s.c.) as an analgesic (21). In the series of experiments reported here, we compared: the analgesic effect of buprenorphine when prepared in two ways in the laboratory with that of a commercially available injectable solution of buprenorphine; the analgesic effect of buprenorphine in Long-Evans rats with that in Sprague-Dawley rats; and Long-Evans and Sprague-Dawley rats for development of pica, a commonly reported side effect of buprenorphine. We followed the pica experiment with assessment of the effectiveness of buprenorphine in establishing a conditioned flavor aversion. The results indicated that method of preparation did not result in any significant differences in the efficacy of injected buprenorphine. Strain of rat was not associated with a significant difference in the efficacy of buprenorphine. However, a significant strain difference was found in development of pica. Buprenorphine treatment was effective in inducing a conditioned flavor aversion. We concluded that the recommended oral dose of buprenorphine (0.5 mg/kg) is ineffective as an analgesic, and that this was not the result of method of preparation of the buprenorphine or strain of rat used. Furthermore, we
concluded that buprenorphine treatment may induce gastrointestinal distress in both strains tested. The results reaffirm our previous conclusion that oral administration of buprenorphine at 0.5 mg/kg, despite the general recommendation, is not a reasonable treatment for postsurgical pain in rats.Dr. Alexis C. ThompsonDr. Mark B. Kristalkristal@buffalo.eduMr. Abdullah SallajMr. Ashley AchesonDr. Lisa B.E. MartinDr. Thomas Martin2007-10-22T10:43:55Z2011-03-11T08:56:59Zhttp://cogprints.org/id/eprint/5771This item is in the repository with the URL: http://cogprints.org/id/eprint/57712007-10-22T10:43:55ZPlacenta ingestion by rats enhances d- and k-opioid antinociception, but suppresses m-opioid antinociceptionIngestion of placenta or amniotic fluid produces a dramatic enhancement of centrally mediated opioid antinociception in the rat. The present experiments investigated the role of each opioid receptor type (m, d, k) in the antinociception-modulating effects of Placental Opioid-Enhancing Factor (POEF—presumably the active substance). Antinociception was measured on a 52 C hotplate in adult, female rats after they ingested placenta or control substance (1.0 g) and after they received an intracerebroventricular injection of a d-specific ([D-Pen2,D-Pen5]enkephalin (DPDPE); 0, 30, 50, 62, or 70 nmol), m-specific ([D-Ala2,N-MePhe4,Gly5-ol]enkephalin (DAMGO); 0, 0.21, 0.29, or 0.39 nmol), or k-specific
(U-62066; spiradoline; 0, 100, 150, or 200 nmol) opioid receptor agonist. The results showed that ingestion of placenta potentiated d- and k-opioid antinociception, but attenuated m-opioid antinociception. This finding of POEF action as both opioid receptor-specific and complex
provides an important basis for understanding the intrinsic pain-suppression mechanisms that are activated during parturition and modified by placentophagia, and important information for the possible use of POEF as an adjunct to opioids in pain management.Jean M. DiPirroDr. Mark B. Kristalkristal@buffalo.edu2003-03-17Z2011-03-11T08:55:14Zhttp://cogprints.org/id/eprint/2836This item is in the repository with the URL: http://cogprints.org/id/eprint/28362003-03-17ZRegulation of Neuromodulator Receptor Efficacy- Implications for Whole-Neuron and Synaptic PlasticityMembrane receptors for neuromodulators (NM) are highly regulated in their distribution and efficacy - a phenomenon which influences the individual cell's response to central signals of NM release.
Even though NM receptor regulation is implicated in the pharmacological action of many drugs, and is also known to be influenced by various environmental factors, its functional consequences and modes of action are not well understood.
In this paper we summarize relevant experimental evidence on NM receptor regulation (specifically dopamine D1 and D2 receptors) in order to explore its significance for neural and synaptic plasticity.
We identify the relevant components of NM receptor regulation (receptor phosphorylation, receptor
trafficking and sensitization of second-messenger pathways)
gained from studies on cultured cells.
Key principles in the regulation and control of short-term plasticity (sensitization) are identified, and a model is presented which employs direct and indirect feedback regulation of receptor efficacy. We also discuss long-term plasticity which involves shifts in receptor sensitivity and loss of responsivity to NM signals.
Finally, we discuss the implications of NM receptor regulation for models
of brain plasticity and memorization.We emphasize that a realistic model of brain plasticity will have to go
beyond Hebbian models of long-term potentiation and depression to include
plasticity in the distribution and efficacy of NM receptors.
Dr. Gabriele Scheler2001-06-20Z2011-03-11T08:54:43Zhttp://cogprints.org/id/eprint/1633This item is in the repository with the URL: http://cogprints.org/id/eprint/16332001-06-20ZDirect Current Auditory Evoked Potentials During Wakefulness, Anesthesia, and Emergence from AnesthesiaDirect current auditory evoked potentials (DC-AEPs)
are a sensitive indicator of depth of anesthesia in ani-mals. However, they have never been investigated in
humans. To assess the potential usefulness of DC-AEPs
as an indicator of anesthesia in humans, we performed
an explorative study in which DC-AEPs were recorded
during propofol and methohexital anesthesia in hu-mans.
DC-AEPs were recorded via 22 scalp electrodes
in 19 volunteers randomly assigned to receive either
propofol or methohexital. DC-AEPs were evoked by
binaurally presented 2-s, 60-dB, 800-Hz tones; meas-urements
were taken during awake baseline, anesthesia,
and emergence. Statistical analysis included analy-sis
of variance and discriminant analysis of data
acquired during these three conditions. About 500 ms
after stimulus presentation, DC-AEPs could be ob-served.
These potentials were present only during base-line
and emergencenot during anesthesia. Statistically
significant differences were found between
baseline and anesthesia and between anesthesia and
emergence. In conclusion, similar effects, as reported in
animal studies of anesthetics on the DC-AEPs, could be
observed in anesthetized humans. These results dem-onstrate
that DC-AEPs are potentially useful in the assessment
of cortical function during anesthesia and
might qualify the method for monitoring anesthesia in
humans.Robert FitzgeraldClaus LammWolfgang OczenskiThomas StimpflWalter VycudilikHerbert Bauer2000-06-14Z2011-03-11T08:53:42Zhttp://cogprints.org/id/eprint/149This item is in the repository with the URL: http://cogprints.org/id/eprint/1492000-06-14ZTHE MIND AND BRAIN SCHOLAR AS A HITCH-HIKER IN POST-GUTENBERG GALAXY: PUBLISHING AT 2000 AND BEYONDElectronic journal (e-journal) publishing has started to change the ways we think about publish-ing. However, many scholars and scientists in the mind and brain sciences are still ignorant of the new possibilities and on-going debates. This paper will provide a summary of the issues in-volved, give an update of the current discussion, and supply practical information on issues re-lated to e- journal publishing and self-archiving relevant for the mind and brain sciences. Issues such as differences between traditional and e-journal publishing, open archive initiatives, world-wide conventions, quality control, costs involved in e-journal publishing, and copyright questions will be addressed. Practical hints on how to self-archive, how to submit to the e-journal Psycolo-quy, how to create an open research archive, and where to find information relevant to e-publishing will be supplied.Brigitte StemmerMarianne CorreYves Joanette2000-05-13Z2011-03-11T08:53:42Zhttp://cogprints.org/id/eprint/147This item is in the repository with the URL: http://cogprints.org/id/eprint/1472000-05-13ZThe study of the regenesis of mind in the 21st centuryThe enigma of consciousness and the brain-mind relationship will - most likely - be unveiled in the 21st century through the new technologies developed at the end of the 20th century and new technologies yet to come. The new technologies will be used to tackle the problem from evolu-tionary, developmental, normal and pathological brain functioning. A major contribution, how-ever, will surface when investigating a particular perspective of pathological brain functioning - a perspective that has not received any attention in the past: the investigation of the re-emergence of mind out of prolonged coma and coma like states.Paul Walter SchönleBrigitte Stemmer2001-10-27Z2011-03-11T08:54:48Zhttp://cogprints.org/id/eprint/1843This item is in the repository with the URL: http://cogprints.org/id/eprint/18432001-10-27ZNeuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancyIntroduction:
Patients with schizophrenia are widely reported to show impairments of attention and neuropsychological performance, but the extent to which this is attributable to medication and dopamine (DA) function remains largely unexplored.
Methods:
We describe here the putative influence of 1) the dose of antipsychotic medication (chlorpromazine equivalents, CPZ), 2) the antipsychotic serum concentration (neuroleptic units in terms of butyrophenone displacement from animal neostriatum) and 3) the approximated DA D2-receptor occupancy in the brain (based on regression curves from 11 studies published for 5 neuroleptics) - - on conditioned blocking (CB) measures of attention and performance on a neuropsycholog-ical battery. We studied 108 patients with schizophrenia with 62 healthy controls.
Results:
1) Antipsychotic serum concentration and D2-occupancy were higher in patients with a paranoid vs. non-paranoid diagnosis, and in female vs. male patients (independent of symptom severity).
2) Controlling for D2-occupancy removed the difference between high CB in paranoid and impaired low CB measures of selective attention in nonparanoid patients.
3) Similar partial correlations for antipsychotic drug dose and serum levels of DA D2-blocking activity with performance on the trail-making and picture completion tests (negative) and the block-design test (positive) showed the functional importance of DA-related activity.
4) High estimates of D2-occupancy were related to impaired verbal fluency - but - were associated with improved recall of stories, especially in paranoid patients.
5) Non-dopaminergic aspects of medication (i.e. CPZ-dependent but not D2-occupancy-associated) impaired verbal recall in males (left-hemisphere function) and non-verbal performance in females (reflecting right hemisphere function).
Conclusions:
This first study of its kind tentatively imputes a role for DA D2-related activity in left frontal (e.g. CB and verbal fluency) and temporal lobe functions (verbal recall), as well as in some non-verbal abilities mediated more in the right hemisphere of patients with schizophrenia
R.D. OadesM.L. RaoS. BenderG. SartoryB.W. Müller1999-07-06Z2011-03-11T08:53:40Zhttp://cogprints.org/id/eprint/105This item is in the repository with the URL: http://cogprints.org/id/eprint/1051999-07-06ZSubmicrosecond pacemaker precision is behaviorally modulated: The gymnotiform electromotor pathwayWhat are the limits and modulators of neural precision? We address this question in the most regular biological oscillator known, the electric organ command in the brainstem of wave-type electric fish. The oscillating electric organ discharge (EOD), used in electrolocation and communication, has high regularity measured by a low coefficient of variation (CV as low as 2 x 10-4) in five species from three families ranging in mean EOD from 70 to 1250 Hz. Intracellular recording in the nucleus (Pn) pacing EODs reveals that individual Pn neurons also display an extremely low CV. While the CV can remain at its minimum for hours, it varies with novel environmental conditions, during communication, and spontaneously. Spontaneous changes occur as abrupt steps (250 msec), oscillations (35 Hz), or slow ramps (1030 sec). Several findings suggest that these changes are under active control and depend on behavioral state. Mean EOD frequency and CV can change independently. CV often decreases in response to stimuli. Lesions of one of the two inputs to the Pn had more influence on CV than lesions of the other inputKatherine T. MoortgatClifford H. KellerTheodore H. BullockTerrence J. Sejnowski2005-02-16Z2011-03-11T08:55:51Zhttp://cogprints.org/id/eprint/4095This item is in the repository with the URL: http://cogprints.org/id/eprint/40952005-02-16ZActivation of G protein-coupled receptors entails cysteine modulation of agonist bindingThe increase of the affinity of agonists with an increase in pH and experiments using thiol-specific reagents indicate that G protein-coupled receptors contain an ionizable cysteine residue at the ligand binding site. Since treatment of receptors with reducing agents produces functional activation and potentiates agonist stimulation, it is likely that this free sulfhydryl modulates receptor activation. We have derived a two-state acid-base model for cysteine modulation of ligand binding which leads to a description of ligand efficacy. We have shown that pH-dependent binding of agonists is closely correlated with measurements of ligand efficacy at the 5-HT2A receptor. In general, efficacy is determined by the preference of a ligand for the base of the receptor. Efficacy may also be described in thermodynamic terms as the coupling free energy involving a ligand and the acid and base states of the receptor. Molecular modeling of the third transmembrane domain of the 5-HT2A receptor, which contains a conserved cysteine, shows that efficacy is determined by the difference between the electrostatic interaction energies of a ligand with the acid and base forms of the receptor model. The difference in interaction energy between the two forms of cysteine makes the largest contribution to this electrostatic interaction energy difference. Therefore, the cysteine makes the largest contribution to ligand efficacy. Using this approach, we can distinquish between the efficacies of agonists with varying molecular structures and account for the differences between the properties of agonists and antagonists.Lester A. RubensteinRichard G. Lanzara2013-05-04T23:21:58Z2013-05-04T23:21:58Zhttp://cogprints.org/id/eprint/8954This item is in the repository with the URL: http://cogprints.org/id/eprint/89542013-05-04T23:21:58ZEffects of cocaethylene on dopamine and serotonin synthesis in Long–Evans and Sprague–Dawley brainsWe examined the behavioral and neurochemical effects of cocaethylene treatment in Long–Evans (�LE). and Sprague–Dawley� (SD) rats. Cocaethylene-induced behaviors were significantly less in LE rats. Cocaethylene caused an inhibition of dopamine synthesis in the caudate nucleus and nucleus accumbens that was equivalent in both rat lines. Serotonin synthesis was also suppressed by cocaethylene treatment, however this phenomenon was less pronounced when compared with the effects on dopamine synthesis.Dr. M.H. BaumannDr. J.M. HorowitzDr. M.B. KristalDr. G. Torres1998-11-14Z2011-03-11T08:53:39Zhttp://cogprints.org/id/eprint/69This item is in the repository with the URL: http://cogprints.org/id/eprint/691998-11-14ZParticipation of Placental Opioid-Enhancing Factor in opioid-modulated events at parturitionParturition in mammals occurs in the context of sensory, neurochemical, and endocrinological factors that are orchestrated and timed so that maternal behavior and the object of the behavior, the neonate, "emerge" almost simultaneously. Among the factors found to be important for the suppression of pain during delivery as well as for the emergence of caretaking behavior toward the young, are changes in endogenous opioid activity in the central nervous system. In most mammalian species, these changes are likely initiated by sensory events arising in the distended reproductive tract and abdominal musculature, and are modified by the parturitional endocrine milieu and substances ingested in amniotic fluid and placenta (e.g., Placental Opioid-Enhancing Factor, or POEF). In addition, ingestion of afterbirth material may decrease the probability that the vaginal/cervical sensory stimulation arising during delivery will trigger pseudopregnancy, a condition that decreases, if not eliminates, the likelihood of fertilization in the postpartum estrus. The research described herein primarily focuses on elucidating the manner in which POEF modulates opioid antinociception, and otherwise participates in opioid-mediated parturitional events.M. B. Kristal2013-05-04T23:21:53Z2013-05-04T23:21:53Zhttp://cogprints.org/id/eprint/8953This item is in the repository with the URL: http://cogprints.org/id/eprint/89532013-05-04T23:21:53ZDifferential Behavioral Responses to
Cocaethylene of Long-Evans and
Sprague-Dawley Rats: Role of SerotoninCocaethylene is a neuroactive metabolite derived from the concurrent consumption of cocaine and ethanol. The effects of cocaethylene on locomotor activity, stereotypy, and rearing in Long-Evans and Sprague-Dawley rats were compared.A single cocaine injection (molar equivalent of 60 μmol/kg cocaethylene, intraperitoneal) elicited a robust series of motor output behaviors, including locomotion, stereotypy, and rearing over a 30-minute testing period in Long-Evans rats. In contrast, cocaethylene administration,
under comparable testing conditions, produced no significant changes in locomotor and investigatory behaviors. Because cocaethylene has relatively little impact on serotonin (5-HT) reuptake as opposed to reuptake of dopamine, we pretreated Long-Evans rats with fluoxetine (10 mg/kg; IP), a selective 5-HT reuptake inhibitor. Fluoxetine profoundly augmented cocaethylene-stimulated behaviors in this rat phenotype. To examine whether other rat strains exhibit a similar response to cocaethylene, Sprague-Dawley rats were injected (IP) with cocaethylene and their behavior patterns monitored over a 30-minute testing period. Cocaethylene produced marked locomotor and exploratory behaviors in this strain, suggesting therefore that Long-Evans and Sprague-
Dawley rats differ in their response to cocaethylene. To relate these behavioral differences to possible structural differences in the neuronal density of dopaminergic or
serotonergic neurons, Long-Evans and Sprague-Dawley brains were evaluated for tyrosine hydroxylase and 5-HT immunocytochemistry. No gross morphological differences
in neuronal architecture or density were found in the ventral tegmental area or dorsal raphe nucleus of the two rat phenotypes. These results indicate that two commonly used rat strains show a differential response to cocaethylene and the neurochemical basis for this behavioral difference may be related to synaptic 5-HT bioavailability.Dr. J.M. HorowitzDr. M.B. Kristalkristal@buffalo.eduDr. G. Torres2013-05-04T23:21:37Z2013-05-04T23:21:37Zhttp://cogprints.org/id/eprint/8952This item is in the repository with the URL: http://cogprints.org/id/eprint/89522013-05-04T23:21:37ZDopaminergic, glutamatergic but not opioidergic mechanisms mediate induction of FOS-like protein by cocaethyleneCocaethylene is a psychoactive metabolite formed
during the combined consumption of cocaine and ethanol. As
this metabolite has many properties in common with cocaine, it is conceivable that cocaethylene administration may induce the activity of nuclear transcription factors that regulate the expression of late-response genes. Therefore, the temporal induction of FOS-like protein in rat brain was examined following IP administration of 60 mmol/kg cocaethylene. Immunoreactivity for the protein was detectable at 1 h in striatal neurons and had virtually disappeared 6 h after drug treatment. Administration of
specific dopaminergic (SCH-23390; 0.5 mg/kg) and glutamatergic (MK-801; 1 mg/kg) receptor antagonists prior to cocaethylene indicated a significant role for dopamine (D1) and Nmethyl-D-aspartate receptor subtypes in mediating the nuclear induction of the aforementioned transcription factor protein. In contrast, no significant effects on FOS-like protein in discrete neurons of the caudate putamen were found when spiradoline (U-62066), a kappa opioid-receptor agonist, was administered either IP (10 mg/kg) or directly (50 nmol) into the brain parenchyma. In addition, we uncovered a differential sensitivity of Long–Evans rats to the behavioral effects of cocaethylene, with the psychoactive metabolite producing significantly less behavioral activity (e.g., locomotion, rearing, and continuous sniffing)than that produced by cocaine (molar equivalent of 60 mmol/kg cocaethylene). These findings indicate both common and disparate effects of cocaethylene and its parent compound, cocaine, on receptor pathways that regulate target alterations in gene expression and drug-induced motor behavior.Dr. J.M. HorowitzDr. J.M. DiPirroDr. M.B. Kristalkristal@buffalo.eduDr. G. Torres2009-01-05T23:58:11Z2011-03-11T08:57:17Zhttp://cogprints.org/id/eprint/6311This item is in the repository with the URL: http://cogprints.org/id/eprint/63112009-01-05T23:58:11ZOpioid stimulation in the ventral tegmental area facilitates the onset of maternal behavior in ratsThis research investigated the effect of an increase or decrease in opioid activity in the ventral tegmental area (VTA) on the onset of maternal behavior in rats. In Experiment 1, the latency to show maternal behavior toward foster rat pups (sensitization latency) was determined in maternally naive female rats given either nothing or a unilateral intra-VTA injection of morphine sulfate (MS) (0.0, 0.01, 0.03, 0.1 or 0.3 µg), on the first three days of a 10-day period of constant exposure to pups. Rats treated with 0.03 µg MS had significantly shorter sensitization latencies than did rats treated with 0.0 µg MS, 0.01 µg MS, or receiving no treatment (higher doses of morphine produced intermediate results). The facilitating effect of intra-VTA MS on the onset of maternal behavior was blocked by pretreatment with naltrexone hydrochloride and was found to have a specific site of action in the VTA (MS injections dorsal to the VTA were ineffective). In Experiment 2, sensitization latencies were determined in periparturitional rats given a bilateral intra-VTA injection of either the opioid antagonist naltrexone methobromide (quaternary naltrexone), its vehicle, a sham injection, or left untreated 40 min after delivery of the last pup. The mothers' own pups were removed at delivery; mothers were nonmaternal at the time of testing. Quaternary naltrexone treatment produced significantly slower sensitization to foster pups than did control conditions. Total activity and pup-directed activity did not differ significantly with treatment. The results demonstrate that increased opioid activity in the VTA facilitates the onset of maternal behavior in inexperienced nonpregnant female rats, and decreased opioid activity in the VTA disrupts the rapid onset of maternal behavior at parturition.Alexis C. ThompsonMark B. Kristal1998-11-14Z2011-03-11T08:53:39Zhttp://cogprints.org/id/eprint/68This item is in the repository with the URL: http://cogprints.org/id/eprint/681998-11-14ZIngestion of amniotic fluid by postpartum rats enhances morphine antinociception without liability to maternal behaviorIngestion of amniotic fluid or placenta by rats has been shown to enhance opioid-mediated analgesia induced by morphine injection, foot shock, vaginal/cervical stimulation, or late pregnancy. The present study was designed to determine whether this mechanism might be a means of providing greater analgesia during the periparturitional period without contributing to the disruption of maternal behavior (measured primarily as retrieval) that can result from excessive opioid levels. Postpartum primiparous rats, injected with either 2 or 3 mg/kg morphine sulfate or vehicle and given orogastric infusions of either amniotic fluid or saline, were tested for maternal behavior. Pain threshold (determined by tail-flick latency test) in rats injected with 2 mg/kg morphine and infused with amniotic fluid was elevated to a level that did not differ significantly from that of a separate group of rats injected with 3 mg/kg morphine and infused with saline. This enhanced analgesia was not, however, accompanied by the significant disruption of maternal behavior found among the rats receiving the higher morphine dose.J. A. TarapackiM. PiechM. B. Kristal2008-09-19T13:55:20Z2011-03-11T08:57:12Zhttp://cogprints.org/id/eprint/6212This item is in the repository with the URL: http://cogprints.org/id/eprint/62122008-09-19T13:55:20ZAmniotic-Fluid Ingestion Enhances
Morphine Analgesia During Morphine
Tolerance and Withdrawal in RatsIngestion of placenta and amniotic fluid has been shown to enhance opioid-mediated analgesia in rats produced by morphine injection. footshock, vaginal/cervical stimulation, and during late pregnancy. The present study was designed to investigate the effects of amniotic fluid ingestion on the characteristics of morphine dependency and withdrawal. Tail-flick latencies in Long-Evans rats were determined before and after repeated daily injections of morphine sulfate. It was found that ingestion of amniotic fluid after establishment of the morphine dependency, coupled with an injection of an otherwise ineffective dose of morphine, enhanced analgesia in morphine-dependent rats, and reversed hyperalgesia seen during withdrawal from morphine dependency.Jean C. DoerrDr. Mark B. Kristalkristal@buffalo.edu2008-09-19T13:55:05Z2011-03-11T08:57:12Zhttp://cogprints.org/id/eprint/6211This item is in the repository with the URL: http://cogprints.org/id/eprint/62112008-09-19T13:55:05ZAmniotic-Fluid Ingestion Enhances the Central
Analgesic Effect of MorphineAmniotic fluid and placenta contain a substance (POEF) that when ingested enhances opioid-mediated analgesia produced by several agents (morphine injection, vaginal/cervical stimulation, late pregnancy, footshock), but not that produced by aspirin injection. The present series of experiments employed quaternary naltrexone, an opioid antagonist that does not readily cross the blood-brain barrier, in conjunction with either peripheral or central administration of morphine, to determine whether amniotic-fluid ingestion (and therefore POEF ingestion) enhances opioid-mediated analgesia by affecting the central and/or peripheral actions of morphine. The results suggest that POEF affects only the central analgesic effects of morphine.Jean M. DiPirrodipirrjm@buffalostate.eduAlexis C. Thompsonathompso@ria.buffalo.eduDr. Mark B. Kristalkristal@buffalo.edu1998-11-15Z2011-03-11T08:53:43Zhttp://cogprints.org/id/eprint/180This item is in the repository with the URL: http://cogprints.org/id/eprint/1801998-11-15ZEnhancement of Opioid-Mediated Analgesia: A Solution to the Enigma of PlacentophagiaTwo major consequences of placentophagia, the ingestion of afterbirth materials that occurs usually during mammalian parturition, have been uncovered in the past several years. The first is that increased contact, associated with ingesting placenta and amniotic fluid from the surface of the young, causes an accelerated onset of maternal behavior toward those young. The second, which probably has importance for a broader range of mammalian taxa than the first, is that ingestion of afterbirth materials produces enhancement of ongoing opioid-mediated analgesia. The active substance in placenta and amniotic fluid has been named POEF, for Placental Opioid-Enhancing Factor. Recent research on both consequences is summarized, with particular attention to POEF, the generalizability of the enhancement phenomenon, its locus and mode of action, and its significance for new approaches to the management of pain and addiction.Mark B. Kristal2007-10-22T10:44:38Z2011-03-11T08:56:59Zhttp://cogprints.org/id/eprint/5769This item is in the repository with the URL: http://cogprints.org/id/eprint/57692007-10-22T10:44:38ZAmniotic-fluid ingestion by parturient rats enhances pregnancy-mediated analgesiaAmniotic fluid and placenta contain a substance (POEF, for Placental Opioid-Enhancing Factor) that, when ingested, enhances opioid-mediated analgesia in nonpregnant rats; ingestion of the substance by rats not experiencing opioid-mediated analgesia, however, does not produce analgesia. It is highly likely that periparturitional analgesia-enhancement is a significant benefit of ingestion of the afterbirth (placentophagia) during delivery. Here we report that prepartum ingestion of amniotic fluid (via orogastric infusion) does indeed enhance the endogenous-opioid-mediated analgesia evident at the end of pregnancy and during delivery; that the degree of enhancement is greater with 0.75 ml than with 0.25 ml, and that the prepartum enhancement of analgesia can be blocked with the opioid antagonist naloxone.Dr. Mark B. Kristalkristal@buffalo.eduAlexis C. ThompsonP. AbbottJean M. DiPirroE.J. FergusonJ. C. Doerr2001-01-24Z2011-03-11T08:54:29Zhttp://cogprints.org/id/eprint/1256This item is in the repository with the URL: http://cogprints.org/id/eprint/12562001-01-24ZEvent-related potentials and monoamines in autistic children on a clinical trial of fenfluramineIntroduction: As autistic persons have problems with selecting and encoding meaningful stimuli and multi-centre studies (Ritvo et al., 1983, 1986) had reported mild behavioural improvements following treatment with fenfluramine, event-related potential (ERP) stages of information processing were studied in childhood autism as part of a double blind crossover study of the efficacy of dl fenfluramine. .
Methods: Acceptable recordings were derived from midline and 4 lateral sites on the scalp of 7 from 14 young persons with autism who understood the task (6 male, 1 female 5.8-17.7 years-of-age). A three-tone oddball paradigm was presented in a passive and active-task form (72% at 1 kHz, 14% at 0.5 kHz and 14% at 2.0 kHz) under placebo and drug conditions (where each condition lasted 5 months). Eleven patients provided blood and urine samples for monoamine analyses in both conditions.
Results:
a) With fenfluramine treatment blood serotonin decreased and urinary catecholamine levels fell (25-45%, but dopamine utilization (HVA/DA) increased 2-4-fold.
b) Under fenfluramine autistic subjects responded non-significantly faster, with fewer errors of omission and improved /decreased beta criterion (signal detection). [IQ measures increased 7.5 points.]
c) N1 amplitudes (Fz) decreased and latencies increased in the fenfluramine condition.
Early negativity (especially on the right) correlated inversely with HVA/DA actvivity.
Subtraction of the ERPs in nontarget from target conditions showed that the Negative difference (Nd) increased during fenfluramine treatment.
d) P3 amplitudes (especially after the deviants) increased with fenfluramine treatment. But in the difference waveform (active-minus-passive condition) the P3 amplitude was halved. The distribution of the P3 component moved rostrally with treatment.
Conclusions: N1 and P3 components of the ERP were responsive to fenfluramine treament. Treatment appears to have mildly improved early stimulus processing at stages represented by the early negative components, but to have mildly impaired processing at the P3-stage. The N1 / Nd - related improvement seems to be related to increased dopamine activity (cf. neuroleptic-like properties of racemate fenfluramine).
R.D. OadesL.M. SternM.K. WalkerC.R. ClarkV. Kapoor2001-04-25Z2011-03-11T08:54:37Zhttp://cogprints.org/id/eprint/1461This item is in the repository with the URL: http://cogprints.org/id/eprint/14612001-04-25ZAttention deficit disorder with hyperactivity (ADDH): the contribution of catecholaminergic activityIntroduction:
An attention deficit disorder with hyperactivity in children (ADDH, later known as ADHD) is now recognized in most countries, although diagnostic practices differ. Evidence is presented to show that the two cardinal symptoms of poor attentional performance and a high degree of motor activity may be functionally and causally separate.
Psychobiology:
Both attentional and motor-activity alterations are temporarily relieved in a proportion of subjects that respond to psychostimulants. Beneficial treatment decreases noradrenergic (NA) metabolism and normalizes variable levels of dopaminergic (DA) metabolism.
Clinical and animal models:
Parallels are drawn with other clinical syndromes arising from changed catecholaminergic activity (cf. Phenylketonuria, Tourette's syndrome, Lesch-Nyhan syndrome) and with behavioral interpretations of the result of damage to the dorsal noradrenergic bundle and dopaminergic VTA A10 nucleus (an animal model).
Biopsychological research directions:
Prognosis of ADDH subjects after treatment remains relatively poor. There may be a further defect of neurotransmitter metabolism in the ADDH syndrome. Research strategies are suggested based on the neurobiological correlates of the cognitive style of ADDH subjects and limbic/septal function in the animal model of the spontaneously hypertensive rat (SHR)
Topics:
1 . Psychostimulant response ... Catecholamines / Serotonin,
2 . Electrophysiological and behavioral indices
3 . Responses to monoaminergic agents ... Precursors, L-DOPA, amino acids, monoamine oxidase and others:
4 . Clinical comparisons ... Phenylketonuria, Tourette's syndrome, Lesch-Nyhan syndrome:
5 . Models ... spontaneously hypertensive rat, neurobiology of hypertension Noradrenaline (NA), Glutamate (Glu), Neuropeptide Y (NPY) & Angiotensin, Serotonin (5-HT), Dopamine (DA):
6 . Link between behavior and cognition ... the septum and conditioned blocking measures of selective attention.
R. D. Oades2001-03-16Z2011-03-11T08:54:36Zhttp://cogprints.org/id/eprint/1371This item is in the repository with the URL: http://cogprints.org/id/eprint/13712001-03-16ZCatecholamines and conditioned blocking: effects of ventral tegmental, septal and frontal 6-hydroxydopamine lesions in ratsIntroduction:
The performance of rats on the conditioned blocking test (CB) of learned inattention was measured in a two-way shuttle avoidance task after sham and dopamine (DA) - depleting lesions of
the frontal cortex,
the limbic septum, and
the ventral tegmental area (VTA - A10).
Methods:
Animals were trained on two sessions with tone and / or light as conditioned stimuli. One group was trained with both stimuli on both sessions. A second group was trained on the first session with one stimulus and on the second with both stimuli. The blocking of conditioning to the added stimulus (b) was tested by presenting the stimuli (a and b) separately and measuring the blocking ration (avoidance to b/a + b) and response latencies.
Results:
1/ No deficits were recorded on tests of sensory and motor ability;
2/ The VTA group alone showed a hyperlocomotor response to apomorphine treatment, - and did not acquire the avoidance response (i.e. did not learn the active avoidance task);
3/ The appearance of blocking in the septally lesioned group was delayed until the end of the 20-trial test session - then it was exaggerated;
4/ Blocking was mildly attenuated in the frontally lesioned group.
5/ Dopamine (DA) levels were depleted by about 80% and noradrenaline (NA) levels by, respectively, 20% and 50% in the frontal and septal regions.
Figure 2 illustrates a) the CB impairment in the frontal group relative to sham controls, and b) the late development of "supr-blocking" in septally-damage animals.
Figure 3 illustrates the results of the HPLC analysis for NA, DA and DOPAC in frontal cortex, septum, N. accumbens and striatum after 6-OHDA lesions (& vehicle treatment) in the frontal, septal, and VTA areas.
Conclusions:
The results show that the levels of DA activity, or rather the balance between the activity of DA and NA in frontal and limbic regions can contribute to efficient associative conditioning and / or the normal ability of rats not to attend to a redundant stimulus.
R.D. OadesJ-M. RivetK. TaghzoutiM. KharoubyH. SimonM. Le Moal2001-03-16Z2011-03-11T08:54:36Zhttp://cogprints.org/id/eprint/1372This item is in the repository with the URL: http://cogprints.org/id/eprint/13722001-03-16ZLocomotor activity in relation to dopamine and noradrenaline in the nucleus accumbens, septal and frontalk areas: a 6-hydroxydopamine studyThe Study and the Method:
The locomotor activity of adult male Sprague-Dawley was automatically recorded in a circular corridor - circadian changes are described as well as the response to the novel situation and its habituation over three hours.
Four groups of animals were compared, - those with sham/vehicle operations and those with 6-OHDA dopamine (DA) depleting lesions in -
the frontal cortex,
the limbic septum, and
the ventral tegmental area (VTA - A10).
Results:
1/ Lesions of the VTA resulted in increased dark-phase activity, - and a large response to an apomorphine challenge in comparison to other lesion and control groups:
2/ Septal 6-OHDA lesions did not alter locomotion:
3/ After frontal DA depletion there was a small increase of locomotion after the apomorphine challenge, that might reflect increased receptor sensitivity in cortical or sub-cortical areas:
(Table 1: HPLC measures of NA, DA and DOPAC for each group in the prefrontal cortex, septum and N. accumbens)
Figure 1 illustrates the cumulative photocell counts per hour over 24 hours for the 4 groups:.
Figure 2 illustrates the cumulative photocell counts every 10 minutes over 90 minutes post-apomorphine treatment - maximal at 20-30 minutes and habituating over 60 minutes (90 minutes for the VTA group): overall activity VTA >> Frontal > Septal > Controls.
Conclusions:
Along with correlations found for motor activity with cortical levels of DA and NA, these results are interpreted to support a role for DA, NA and the region of the frontal cortex in modulating locomotion that is primarily mediated by mesolimbic VTA - accumbens - DA activity.
R.D. OadesK. TaghzoutiJ-M. RivetH. SimonM. Le Moal2001-04-05Z2011-03-11T08:54:37Zhttp://cogprints.org/id/eprint/1435This item is in the repository with the URL: http://cogprints.org/id/eprint/14352001-04-05ZDopamine-sensitive alternation and collateral behaviour in a Y-maze: effects of d-amphetamine and haloperidolIntroduction:
The frequency of spontaneous alternation in a Y-maze (visiting each arm in turn at p>50%) depends on the influence of the attention given to intra- and extra-maze cues.
We examined the observing responses shown by rats (collateral rearing and head-turning behaviour), the habituation to the novelty and alternation responses over 15 minutes/day, four days in a row - in a Y-maze under enhanced and reduced dopamine (DA) activity (amphetamine- and haloperidol treatment).
Methods:
Prior to placement in a Y-maze for 15 minutes observation on 4 successive days animals were treated with either amphetamine (0.5 or 2.5 mg/kg) or pre-treated with a low dose of haloperidol (0.08 mg/kg, ip).
Results:
1/ Amphetamine treated animals chose the arms at random on day 1, but after the higher dose on day 2-4 they perseverated their choice. The controls maintained their alternation over this period.
2/ The amphetamine-induced effects on alternation were prevented by prior treatment with the neuroleptic haloperidol.
3/ Amphetamine treatment increased the frequency of rearing in the middle at the choice point of the Y-maze. Haloperidol pre-treatment blocked this increase at the midpoint on day 1, and blocked the rearing behavior at the end of an arm on day 2.
4/ Amphetamine also increased the frequency of head turning and "looking", - an effect that was also prevented by haloperidol. (day 2 onwards).
5/ Haloperidol increased the duration of" looking" and of rearing at the end of an arm later in testing..
Conclusions:
Two effects are postulated to have occurred.
a) a conflict on day 1 between the novelty-controlled sensory or attentional effects, that leads to an alternation of arm-choice, and amphetamine-induced DA activity that facilitates an alternation of behavioural responses: -- the result was random choice and increased rearing at the choice point.
b) On days 2-4 the drug-induced effects on switching motor responses came to control behaviour
R.D. OadesK. TaghzoutiH. SimonM. Le Moal2001-05-08Z2011-03-11T08:54:37Zhttp://cogprints.org/id/eprint/1481This item is in the repository with the URL: http://cogprints.org/id/eprint/14812001-05-08ZDopaminergic agonistic and antagonistic drugs in the ventral tegmentum of rats inhibit and facilitate changes of food-search behaviourIntroduction:
The proposal that an increase of dopaminergic (DA) activity in the mesocorticolimbic pathway with an origin in the ventral tegmental area (VTA A10) increases the probability of behavioural change was tested (Koob et al., 1978 - see also Oades, 1985 on the switching role of DA)
Methods:
Food-deprived animals searched for food pellets placed consistently in 4 holes of a 16-hole-board. They were presented with 9 sessions of 10 trials/session. Groups of rats received lesions of the VTA or injections of the DA D2 antagonist spiroperidol (2µg/0.5 µl) or the DA agonist apomorphine (2 µg(0.5µl) into the VTA before sessions 4 and 7.
[Neuroleptic treatment should block local inhibition via autoreceptors and thus lead to increased DA activity in the terminal regions]
Results:
1/ Compared to vehicle- or apomorphine-treatment, spiroperidol increased the number of empty hole-visits (errors)
2/ Comparison animals (vehicle- and apomorphine treated) developed individually specific but consistent sequences of hole-visits ("strategy") -- these were disrupted on sessions 4 and 7 after neuroleptic treatment and following VTA damage.
(i.e. there was much intra-session switching between sequences from trial to trial.)
3/ Further the identity of the preferred sequence on session 7 was more often different than on session 4 for lesioned and neuroleptic treated animals than for the comparison groups.
(i.e there was also inter-session switching between sequences between sessions 4 and 7.)
4/ Although many apomorphine-treated animals changed their preference on session 4, this was not repeated after the second treatment on session 7 - when fewer changes were recorded than for the controls..
Conclusions:
.The results are consistent with increased switching of strategies in animals with increased mesocorticolimbic DA activity - where the learning and maintenance of strategies are seen as an aid to recall the adaptive sequence of behaviour likely to lead to the relevant baited holes.
Oades2001-05-16Z2011-03-11T08:54:38Zhttp://cogprints.org/id/eprint/1503This item is in the repository with the URL: http://cogprints.org/id/eprint/15032001-05-16ZImpairments of search behaviour in rats after haloperidol treatment, hippocampal or neocortical damage suggest a mesocorticolimbic role in cognitionIntroduction:
In view of reports that fimbria-fornix or hippocampal lesions impair working rather than reference memory in a radial maze (Olton et al., 1979) the performance of rodents with hippocampal damage was examined on a hole-board search task.
Methods:
Food-deprived animals searched for food pellets placed consistently in 4 holes of a 16-hole-board (figure 1). They were presented with 11 sessions of 10 trials/session. There were three groups of animals, - one with aspiration lesions of the hippocampus and overlying neocortex, one with damage only to the overlying neocortex and sham-controls that went through the procedure but the brain was left intact (Oades and Isaacson, 1978). Half of each group received haloperidol (0.275 mg/kg) or saline injections 15 minutes before each of the sessions 4-10.
Working memory error = a visit to a correct hole that has just been visited, and thus no longer contains a food pellet.
Reference memory error = visit to a hole that is never baited.
Results:
1/ Hippocampal damage resulted in poorer performance on both working and reference memory measures: this was unaffected by haloperidol treatment.
2/ Neuroleptic treatment also impaired the performance of the sham-controls on both measures.
3/ Animals with neocortical damage were impaired on reference mmeory measures alon, after haloperidol treatment.
Conclusions:
.The lack of a neuroleptic effect on performance after hippocampal damage suggests that this lesion does not impair performance on these two measures of memory performance through a dopaminergic mechanism.
Haloperidol impaired working memory measures in sham-controls, but only reference memory measures in the neocortical group.. The results imply that there are (at least) three separate mechanisms (i.e. meso-cortico-limbic interactions) at work here involved in shorter- and longer-term consolidation of the consequences of selective attention mechanism required to efficiently learn a search task. Oades2001-05-29Z2011-03-11T08:54:39Zhttp://cogprints.org/id/eprint/1521This item is in the repository with the URL: http://cogprints.org/id/eprint/15212001-05-29ZThe development of food search behavior by rats: the effects of hippocampal damage and haloperidolIntroduction:
The aim of the study was to see if some of the effects of hippocampal brain damage on attention-related function may be mediated perhaps trans-synaptically in the dopamine (DA) system.
Methods:
A food search task in a 16-hole board was developed (based on search studies used to investigate the avian hippocampus (Oades 1976), but suitable for rodents). Food-deprived rats were required to locate 4 pellets located in 4 of 16 holes in an enclosed arena.
Three groups of animals were studied in 11 test sessions : - rats with bilateral hippocampal aspiration lesions, bilateral neocortical damage (overlying the hippocampus), and an unoperated group. Half of each group received haloperidol (DA D2 antagonist) and half saline before sessions 4 through 10. No injections were administered on the first three or the last test session.
Results:
1/ Animals with hippocampal damage visited more non-food holes (errors) than the controls, AND did not develop consistent sequences of food-hole visits as the other animals did.
2/ In unoperated controls haloperidol reduced the number of preferred sequences of food-hole visits, WITHOUT affecting the efficiency of performance as measured by the number of non-food-holes visited (i.e., the number of errors did not increase).
3/ Haloperidol treatment of those with hippocampal damage
reduced the number of non-food-hole visits (i.e. reduced the number of errors made in comparison to the saline treated animals with hippocampal damage).
Conclusions:
It is likely that hippocampal damage incurs increased DA activity elsewhere that for the search task is not adaptive and brings about an increase in the number of errors made. This contrasts with the normal development of a consistent sequence of food-hole visits (individually specific) - one form of working memory aid - that is disrupted by haloperidol and by hippocampal damage. Neuroleptic treatment of the hippocampal animals did not reinstate this preferred sequence but by dampening DA activity (reducing switching between alternatives, Oades 1985) improved attention-related search performance by decreasing the number of erros made.
This result may be seen post-hoc as a model for some of the functions disturbed in schizophrenia - where there is evidence for impaired medial temporal lobe function (hippoicampus, parahippocampal gyrus) and often hyper-active DA systems, sometimes ameliorated through neuroleptic treatment (see further studies by Lipska and Weinberger: e.g. Lipska et al. 1992; 1993, 1994, 1995; Sams-Dodd et al., 1997; Wood et al., 1997).
Oades Isaacson2001-06-26Z2011-03-11T08:54:43Zhttp://cogprints.org/id/eprint/1637This item is in the repository with the URL: http://cogprints.org/id/eprint/16372001-06-26ZThe effect of unilateral 6-hydroxydopamine lesions in the substantia nigra on hippocampal noradrenaline-induced feeding and other behaviour in the ratIntroduction:
Given that administration of noradrenaline (NA) to the cerebral ventricles or into the hippocampus can elicit feeding, and that lesion the the dopaminergic (DA) substantia nigra (SN) can bring about aphagia, the present report considers the interaction of these two manipulations.
Methods:
Cannulae were implanted into the SN and the dorsal hippocampus of rats kept on a normal food and water regimen.
One week after surgery 13 µg NA in 0.6 µl were administered to the hippocampus and the animals were observed for 20 minutes or until 3 minutes had elapsed after feeding had stopped.
The behavioural effects of 6-hydroxydopamine lesions of the SN were recorded from a circular open arena.
Results:
1/ Feeding in short bouts was elicited after NA injection to 25/30 sites in the hippocampus
2/ More feeding was observed from sites where later histology suggested there had been no leakage to the ventricles (88%). The feeding behavior did not result from spreading depression (>7 shakes recorded on 3% of tests).
3/ After SN lesion, NA still elicited feeding from all hippocampal sites (on two or more occasions).
4/ The SN lesion did not alter the latency to feed, the duration of feeding or the intake of food. (A temporary decrease of body weight was registered on the third postoperative day, only).
5/ NA treatment did not affect locomotion (pre- or post-lesion) although the lesion on its own increased the latency to move and rotation in the open field.
Conclusions:
Unilateral SN-6-OHDA treatment did not affect feeding elicited by ipsi- or contralateral hippocampal teatment with NA.
It is suggested that 6-OHDA induced hypophagia may result from non-specific effects of treatment as the latencies to rest, the duration of grooming increased and feeding bout-duration decreased following the injection of vehicle or toxin.
Oades2001-05-29Z2011-03-11T08:54:39Zhttp://cogprints.org/id/eprint/1520This item is in the repository with the URL: http://cogprints.org/id/eprint/15202001-05-29Zp-Chlorophenylalanine-produced effects on behavior in intact and brain-damaged ratsIntroduction:
Our aim was to determine if a reduction of serotonin (5-HT) synthesis in the brain would provide any protection from the behavioral alterations induced by hippocampal brain-damage. The development of open-field activity (5 minute sessions) over two weeks and the acquisition of a passive avoidance task were chosen for study.
Methods:
There were 3 groups of lesioned rats - those hippocampal aspiration lesions, those with only damage to the neocortex overlying the hippocampus, and a sham-operated group. Half of each group was treated 300 mg/kg p-chlorphenylalanine (PCPA) for 3 successive days to deplete levels of 5-HT and the other half were given the saline vehicle alone.
[Hippocampal damage is associated with increased activity in the open field and impaired learning of the step-through passive avoidance response.]
Results:
1/ Animals with hippocampal damage became hyperactive in the second week after operation.
2/ PCPA treatment had no effect on locomotion, (nor on the frequently observed thigmotaxic nature of the behavior)
3/ Rearing was initially depressed after the operation, and PCPA treatment facilitated its recovery - but PCPA decreased rearing in intact animals during the second week of testing.
4/ Reduced levels of grooming were seen in hippocampal animals, while PCPA reduced grooming in those with neocortical damage
5/ The animals with hippocampal damage were impaired in witholding response in the passive avoidance task - those treated with PCPA performed even worse in not witholding the shock-reinforced step-through response. This contrasted with the intact animals, where PCPA treatment reduced the amount of footshock the animals were exposed to in the task
Conclusions:
.The results are consistent with a role for mesolimbic 5-HT innervation of the dorsal hippocampus having an influence on novelty-elicited responses (e.g. grooming in home vs. novel cage and investigative rearing behavior) and in modulation of the sensitivity of response to electric footshock (hypersensitive in PCPA-intact animals, hyposensitive in PCPA-hippocampal animals).
R.D. Oades Isaacson