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

The present study compares, using a double-blind, placebo controlled design the effects of two alpha 2-agonists, clonidine (0.5, 2, and 5 mu g/kg) and guanfacine (7 and 29 mu g/kg) on spatial working memory, planning and atte ntional set-shiffing, fractions thought to be dependent on the "central exe cutive" of the prefrontal cortex. Blood pressure and the subjective feeling of sedation were affected equally by clonidine and guanfacine. The 0.5 mu g/kg and 5 mu g/kg doses of clonidine disrupted spatial working memory, but the medium dose had no effect. The 0.5 and 2 mu g/kg doses of clonidine in creased impulsive responding in the planning test. The 5 mu g/kg dose of cl onidine slowed responding at effortful levels of planning and attentional s et-shifting tests. The 29 mu g/kg dose of guanfacine improved spatial worki ng memory and planning. Guanfacine had no effect on attentional set-shiftin g. These data indicate that guanfacine improved planning and spatial workin g memory, but clonidine dose-dependently disrupted performance. It is possi ble that the greater selectivity of guanfacine for alpha 2A-subtype may und erlie its differences from clonidine. (C) 1999 American College of Neuropsy chopharmacology. Published by Elsevier Science Inc.