The Experts below are selected from a list of 111 Experts worldwide ranked by ideXlab platform
Robert H Roth - One of the best experts on this subject based on the ideXlab platform.
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enduring cognitive deficits and cortical dopamine dysfunction in monkeys after long term administration of Phencyclidine
Science, 1997Co-Authors: J D Jentsch, Kenneth D Youngren, D E Redmond, John D Elsworth, Jane R Taylor, Robert H RothAbstract:The effects of the psychotomimetic drug Phencyclidine on the neurochemistry and function of the prefrontal cortex in vervet monkeys were investigated. Monkeys treated with Phencyclidine twice a day for 14 days displayed performance deficits on a task that was sensitive to prefrontal cortex function; the deficits were ameliorated by the atypical antipsychotic drug clozapine. Repeated exposure to Phencyclidine caused a reduction in both basal and evoked dopamine utilization in the dorsolateral prefrontal cortex, a brain region that has long been associated with cognitive function. Behavioral deficits and decreased dopamine utilization remained after Phencyclidine treatment was stopped, an indication that these effects were not simply due to direct drug effects. The data suggest that repeated administration of Phencyclidine in monkeys may be useful for studying psychiatric disorders associated with cognitive dysfunction and dopamine hypofunction in the prefrontal cortex, particularly schizophrenia.
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subchronic Phencyclidine administration reduces mesoprefrontal dopamine utilization and impairs prefrontal cortical dependent cognition in the rat
Neuropsychopharmacology, 1997Co-Authors: J D Jentsch, A Tran, Kenneth D Youngren, Robert H RothAbstract:Repeated ingestion of Phencyclidine by humans induces enduring schizophrenic symptomatology, particularly cognitive dysfunction. In the presently described series of experiments, the neurochemical and cognitive consequences of subchronic Phencyclidine administration in the rat were explored. Repeated Phencyclidine exposure led to a selective reduction in basal and stress-evoked dopamine utilization in the prefrontal cortex. In addition, rats previously subchronically-treated with Phencyclidine were impaired on performance of a spatial working memory task in a delay-dependent manner. Importantly, these dopaminergic and cognitive deficits were observed after withdrawal from Phencyclidine, and as such, the neurochemical and behavioral effects were due to drug-induced neurobiological changes rather than direct drug effects. These biochemical and behavioral data show that repeated Phencyclidine administration induces prefrontal cortical cognitive deficits in rats, as in humans, and offer a biochemical perspective of the neural substrate underlying this cognitive impairment: inhibition of mesocortical dopamine neurons. Thus, these data may have relevance to psychiatric disorders involving prefrontal cortical dopaminergic hypoactivity and cognitive dysfunction, as has been hypothesized in schizophrenia.
Li M - One of the best experts on this subject based on the ideXlab platform.
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Effects of drugs on concurrent variable-interval variable-interval schedule performance.
Behavioural pharmacology, 1998Co-Authors: Donald E. Mcmillan, Li MAbstract:According to the generalized matching law the ratio of responses between two alternatives matches the ratio of reinforcers produced by these responses. In these experiments using concurrent variable-interval variable-interval schedules in pigeons, responding occurred more frequently on the key associated with the lower reinforcement density (undermatching) than would be predicted by perfect matching. Under control conditions, there was no bias toward responding on either key. Pentobarbital, methamphetamine, morphine and phencylidine all increased bias toward responding on the left key with the exception of one 10 mg/kg dose of pentobarbital that increased bias toward responding on the right key. Higher doses of methamphetamine and morphine, and most doses of Phencyclidine increased matching, but high doses of pentobarbital further decreased matching. Morphine increased bias toward responding on the left key at much lower doses than those that affected matching, while Phencyclidine increased matching at lower doses than those that increased bias. Pentobarbital produced small increases in response rates that were sometimes accompanied by small increases in key switching. All other drugs only decreased response rate and decreased the number of key switches. These data suggest that drugs disrupt responding under concurrent schedules both by increasing bias and by changing baseline matching functions.
J D Jentsch - One of the best experts on this subject based on the ideXlab platform.
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enduring cognitive deficits and cortical dopamine dysfunction in monkeys after long term administration of Phencyclidine
Science, 1997Co-Authors: J D Jentsch, Kenneth D Youngren, D E Redmond, John D Elsworth, Jane R Taylor, Robert H RothAbstract:The effects of the psychotomimetic drug Phencyclidine on the neurochemistry and function of the prefrontal cortex in vervet monkeys were investigated. Monkeys treated with Phencyclidine twice a day for 14 days displayed performance deficits on a task that was sensitive to prefrontal cortex function; the deficits were ameliorated by the atypical antipsychotic drug clozapine. Repeated exposure to Phencyclidine caused a reduction in both basal and evoked dopamine utilization in the dorsolateral prefrontal cortex, a brain region that has long been associated with cognitive function. Behavioral deficits and decreased dopamine utilization remained after Phencyclidine treatment was stopped, an indication that these effects were not simply due to direct drug effects. The data suggest that repeated administration of Phencyclidine in monkeys may be useful for studying psychiatric disorders associated with cognitive dysfunction and dopamine hypofunction in the prefrontal cortex, particularly schizophrenia.
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subchronic Phencyclidine administration reduces mesoprefrontal dopamine utilization and impairs prefrontal cortical dependent cognition in the rat
Neuropsychopharmacology, 1997Co-Authors: J D Jentsch, A Tran, Kenneth D Youngren, Robert H RothAbstract:Repeated ingestion of Phencyclidine by humans induces enduring schizophrenic symptomatology, particularly cognitive dysfunction. In the presently described series of experiments, the neurochemical and cognitive consequences of subchronic Phencyclidine administration in the rat were explored. Repeated Phencyclidine exposure led to a selective reduction in basal and stress-evoked dopamine utilization in the prefrontal cortex. In addition, rats previously subchronically-treated with Phencyclidine were impaired on performance of a spatial working memory task in a delay-dependent manner. Importantly, these dopaminergic and cognitive deficits were observed after withdrawal from Phencyclidine, and as such, the neurochemical and behavioral effects were due to drug-induced neurobiological changes rather than direct drug effects. These biochemical and behavioral data show that repeated Phencyclidine administration induces prefrontal cortical cognitive deficits in rats, as in humans, and offer a biochemical perspective of the neural substrate underlying this cognitive impairment: inhibition of mesocortical dopamine neurons. Thus, these data may have relevance to psychiatric disorders involving prefrontal cortical dopaminergic hypoactivity and cognitive dysfunction, as has been hypothesized in schizophrenia.
Anthony A. Grace - One of the best experts on this subject based on the ideXlab platform.
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Phencyclidine interferes with the hippocampal gating of nucleus accumbens neuronal activity in vivo
Neuroscience, 1998Co-Authors: Patricio O'donnell, Anthony A. GraceAbstract:Abstract The N -methyl- d -aspartate channel blocker Phencyclidine is known to induce psychotic episodes in normal subjects and exacerbate psychosis in schizophrenics; however, its site of action is not clear. The prefrontal cortex, hippocampus, and basal ganglia are brain regions that appear to play a role in the pathophysiology of schizophrenia, and therefore are the most likely to be involved in the psychotomimetic action of Phencyclidine. In this study, systemic administration of Phencyclidine reduced the frequency and duration of the spontaneously occurring depolarized plateaus observed in the membrane potential of accumbens neurons recorded intracellularly in vivo . Furthermore, recordings from rats pretreated with Phencyclidine yielded proportionately fewer neurons showing depolarized events compared with untreated animals. These results suggest that Phencyclidine may interfere with the generation of the depolarized (“up”) state of the accumbens neuron membrane potential, which we had previously shown is dependent upon hippocampal input and is necessary for action potential discharge in these neurons. This action of Phencyclidine is proposed to impair the flow of cortical information through the nucleus accumbens, and thereby mimic the consequences of the hippocampal deficit proposed to contribute to the pathophysiology of schizophrenia.
Donald E. Mcmillan - One of the best experts on this subject based on the ideXlab platform.
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Effects of drugs on concurrent variable-interval variable-interval schedule performance.
Behavioural pharmacology, 1998Co-Authors: Donald E. Mcmillan, Li MAbstract:According to the generalized matching law the ratio of responses between two alternatives matches the ratio of reinforcers produced by these responses. In these experiments using concurrent variable-interval variable-interval schedules in pigeons, responding occurred more frequently on the key associated with the lower reinforcement density (undermatching) than would be predicted by perfect matching. Under control conditions, there was no bias toward responding on either key. Pentobarbital, methamphetamine, morphine and phencylidine all increased bias toward responding on the left key with the exception of one 10 mg/kg dose of pentobarbital that increased bias toward responding on the right key. Higher doses of methamphetamine and morphine, and most doses of Phencyclidine increased matching, but high doses of pentobarbital further decreased matching. Morphine increased bias toward responding on the left key at much lower doses than those that affected matching, while Phencyclidine increased matching at lower doses than those that increased bias. Pentobarbital produced small increases in response rates that were sometimes accompanied by small increases in key switching. All other drugs only decreased response rate and decreased the number of key switches. These data suggest that drugs disrupt responding under concurrent schedules both by increasing bias and by changing baseline matching functions.
