The alpha-2A-adrenoceptor agonist, guanfacine, increases regional cerebralblood flow in dorsolateral prefrontal cortex of monkeys performing a spatial working memory task

Research indicates that norepinephrine enhances the working memory function s of the prefrontal cortex (PFC) through actions at post-synaptic, alpha-2A adrenoceptors. The current study examined the effects of the alpha-2A adre noreceptor agonist, guanfacine (0.7 mg/kg, i.m.), compared to saline on SPE CT measures of regional cerebral blood flow (rCBF) in monkeys performing a spatial working memory task. Animals were infused with the SPECT blood flow tracer, Tcm-99m ECD, through an indwelling intravenous catheter while perf orming the working memory task. Guanfacine treatment significantly improved cognitive performance of the working memory task, and significantly increa sed rCBF values in the dorsolateral PFC, the brain region most tightly asso ciated with performance of spatial working memory tasks. In contrast, guanf acine had no significant effect on rCBF in the superior temporal cortex, an auditory association area unrelated to task performance. These data are co nsistent with the hypothesis that alpha-2A adrenoceptor stimulation prefere ntially enhances functioning of the PFC. (C) 2000 American College of Neuro psychopharmacology. Published by Elsevier Science Inc. All rights reserved.