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Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys
B L Murphy1, A F Arnsten, P S Goldman-Rakic
1Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510-8001, USA.
Summary
Mild stress and FG7142 increase prefrontal cortex dopamine, impairing spatial working memory in rats and monkeys. This cognitive deficit is linked to dopamine activity and reversed by antagonists.
Area of Science:
- Neuroscience
- Cognitive Science
- Pharmacology
Background:
- Mild stress selectively activates the prefrontal cortical dopamine system.
- Anxiogenic beta-carbolines, like FG7142, mimic this stress-induced dopamine activation.
- Understanding the role of prefrontal dopamine in cognition is crucial.
Purpose of the Study:
- To investigate the functional relevance of elevated prefrontal cortex dopamine turnover.
- To examine the effects of FG7142 on spatial working memory in rats and monkeys.
Main Methods:
- Administered FG7142 to rats and monkeys performing spatial working memory tasks.
- Measured prefrontal cortical dopamine turnover biochemically in rats.
- Utilized receptor antagonists (benzodiazepine and dopamine) to block FG7142 effects.
Main Results:
- FG7142 selectively increased prefrontal cortical dopamine turnover in rats.
- FG7142 significantly impaired spatial working memory performance in both species.
- Cognitive deficits correlated positively with prefrontal cortex dopamine turnover in rats.
- Antagonist pretreatment prevented FG7142-induced deficits and dopamine changes.
Conclusions:
- Excessive dopamine activity in the prefrontal cortex is detrimental to cognitive functions.
- Prefrontal cortex dopamine system modulation impacts executive functions like working memory.
- FG7142 serves as a valuable tool for studying the neurobiology of working memory deficits.