Subchronic Phencyclidine Administration Reduces Mesoprefrontal Dopamine Utilization and Impairs Prefrontal Cortical-Dependent Cognition in the Rat (original) (raw)

Neuropsychopharmacology volume 17, pages 92–99 (1997)Cite this article

Abstract

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.

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  1. From the the Interdepartmental Neuroscience Progam, and Departments of Pharmacology and Psychiatry, Section of Neurobiology, Yale University School of Medicine, New Heaven, Connecticut
    J David Jentsch BA, Anh Tran BA, Dung Le BA, Kenneth D Youngren M.Phil & Robert H Roth Ph.D

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  1. J David Jentsch BA
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  2. Anh Tran BA
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  3. Dung Le BA
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  4. Kenneth D Youngren M.Phil
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  5. Robert H Roth Ph.D
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Jentsch, J., Tran, A., Le, D. et al. Subchronic Phencyclidine Administration Reduces Mesoprefrontal Dopamine Utilization and Impairs Prefrontal Cortical-Dependent Cognition in the Rat.Neuropsychopharmacol 17, 92–99 (1997). https://doi.org/10.1016/S0893-133X(97)00034-1

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