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

Biol Psychiatry. 1999 Nov 1;46(9):1259-65. doi: 10.1016/s0006-3223(99)00139-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Agonists*
  • Adrenergic alpha-2 Receptor Agonists*
  • Adrenergic alpha-Agonists / administration & dosage
  • Adrenergic alpha-Agonists / adverse effects
  • Adrenergic alpha-Agonists / pharmacology*
  • Animals
  • Female
  • Guanfacine / administration & dosage
  • Guanfacine / pharmacology*
  • Infusions, Parenteral
  • Macaca mulatta
  • Male
  • Memory, Short-Term / drug effects*
  • Norepinephrine / metabolism*
  • Phenylephrine / administration & dosage
  • Phenylephrine / adverse effects*
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / surgery
  • Spatial Behavior / drug effects*

Substances

  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-2 Receptor Agonists
  • Adrenergic alpha-Agonists
  • Phenylephrine
  • Guanfacine
  • Norepinephrine