Local infusion of an alpha-1 adrenergic agonist into the prefrontal corteximpairs spatial working memory performance in monkeys

Background: Stimulation of alpha-2 adrenoceptors in the monkey or rat prefr ontal cortex (PFC) has been known to improve spatial working memory (SWM) a nd stimulation of alpha-1 adrenoceptors in the rat PFC has been reported to impair SWM. The present study attempted to replicate in monkey the rat exp eriments on alpha-1 adrenoceptor stimulation. Methods: The alpha-1 adrenergic agonist phenylephrine or the alpha-2 adrene rgic agonist guanfacine was infused into the dorsolateral prefrontal cortex (dlPFC) of monkeys performing the delayed-response (DR) task, a task of SW M, to see how the drugs affect SWM performance. Results: Phenylephrine infusion in dlPFC significantly impaired DR performa nce, whereas guanfacine improved performance. The effects of both drugs wer e delay-dependent. Infusions outside dlPFC were ineffective. Conclusions: Stimulation of prefrontal cortical alpha-1 adrenoceptors impai rs SWM function in monkeys, consistent with the parallel study in vats, whe reas stimulation of alpha-2 adrenoceptors improves SWM, indicating that alp ha-1 and alpha-2 adrenoceptors may have opposing roles in the PFC. (C) 1999 Society of Biological Psychiatry.