Guanfacine, but not clonidine, improves planning and working memory performance in humans

Abstract

The present study compares, using a double-blind, placebo controlled design the effects of two α2-agonists, clonidine (0.5, 2, and 5 μg/kg) and guanfacine (7 and 29 μg/kg) on spatial working memory, planning and attentional set-shifting, functions thought to be dependent on the 'central executive' of the prefrontal cortex. Blood pressure and the subjective feeling of sedation were affected equally by clonidine and guanfacine. The 0.5 μg/kg and 5 μg/kg doses of clonidine disrupted spatial working memory, but the medium dose had no effect. The 0.5 and 2 μg/kg doses of clonidine increased impulsive responding in the planning test. The 5 μg/kg dose of clonidine slowed responding at effortful levels of planning and attentional set-shifting tests. The 29 μg/kg dose of guanfacine improved spatial working memory and planning. Guanfacine had no effect on attentional set-shifting. These data indicate that guanfacine improved planning and spatial working memory, but clonidine dose-dependently disrupted performance. It is possible that the greater selectivity of guanfacine for α2A-adrenoceptor subtype may underlie its differences from clonidine. Copyright (C) 1999 American College of Neuropsychopharmacology.