NDLI: Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys.

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Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys.

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Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Murphy, B. L. Arnsten, A. F. Roth, R. H. Goldman-rakic, P. S.
Description	Author Affiliation: Murphy BL ( Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510-8001, USA.);
Abstract	The selective activation of the prefrontal cortical dopamine system by mild stress can be mimicked by anxiogenic beta-carbolines such as FG7142. To investigate the functional relevance of elevated levels of dopamine turnover in the prefrontal cortex, the current study examined the effects of FG7142 on the performance of spatial working memory tasks in the rat and monkey. FG7142 selectively increased prefrontal cortical dopamine turnover in rats and significantly impaired performance on spatial working memory tasks in both rats and monkeys. Spatial discrimination, a task with similar motor and motivational demands (rats), or delayed response performance following zero-second delays (monkeys) was unaffected by FG7142. Further, biochemical analysis in rats revealed a significant positive correlation between dopamine turnover in the prefrontal cortex and cognitive impairment on the delayed alternation task. The cognitive deficits in both rats and monkeys were prevented by pretreatment with the benzodiazepine receptor antagonist, RO15-1788, which blocked the increase in dopamine turnover and by the dopamine receptor antagonists, haloperidol, clozapine, and SCH23390. These findings indicate that excessive dopamine activity in the prefrontal cortex is detrimental to cognitive functions mediated by the prefrontal cortex.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	3
Volume Number	93
Language	English
Publisher	National Academy of Sciences
Publisher Date	1996-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Carbolines Pharmacology Dopamine Metabolism Maze Learning Physiology Memory Motor Activity Drug Effects Prefrontal Cortex Space Perception Analysis Of Variance Animals Benzazepines Clozapine Dopamine Antagonists Flumazenil GABA Modulators GABA-A Receptor Antagonists Haloperidol Macaca Mulatta Rats, Sprague-Dawley Stress, Psychological Comparative Study Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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