Local infusion of an alpha-1 adrenergic agonist into the prefrontal cortex impairs spatial working memory performance in monkeys.
BACKGROUND
Stimulation of alpha-2 adrenoceptors in the monkey or rat prefrontal cortex (PFC) has been known to improve spatial working memory (SWM) and 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 experiments on alpha-1 adrenoceptor stimulation.


METHODS
The alpha-1 adrenergic agonist phenylephrine or the alpha-2 adrenergic agonist guanfacine was infused into the dorsolateral prefrontal cortex (dlPFC) of monkeys performing the delayed-response (DR) task, a task of SWM, to see how the drugs affect SWM performance.


RESULTS
Phenylephrine infusion in dlPFC significantly impaired DR performance, whereas guanfacine improved performance. The effects of both drugs were delay-dependent. Infusions outside dlPFC were ineffective.


CONCLUSIONS
Stimulation of prefrontal cortical alpha-1 adrenoceptors impairs SWM function in monkeys, consistent with the parallel study in rats, whereas stimulation of alpha-2 adrenoceptors improves SWM, indicating that alpha-1 and alpha-2 adrenoceptors may have opposing roles in the PFC.
Mao
Z M
ZM
Key Laboratory of Neurobiology, Shanghai Institute of Physiology, Chinese Academy of Sciences, People's Republic of China.
Arnsten
A F
AF
Li
B M
BM
D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D005260:Female; D016316:Guanfacine / Q000008:administration & dosage / Q000494:pharmacology*; D007263:Infusions, Parenteral; D008253:Macaca mulatta; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism*; D010656:Phenylephrine / Q000008:administration & dosage / Q000009:adverse effects*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000601:surgery; D013037:Spatial Behavior / Q000187:drug effects*
D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D010656:Phenylephrine; D016316:Guanfacine; D009638:Norepinephrine