Guanfacine and clonidine, alpha2-agonists, improve paired associates learning, but not delayed matching to sample, in humans

The present study compares the effects of two alpha2-agonists, clonidine (0.5, 2, and 5 mu g/kg, PO) and guanfacine (7 and 29 mu g/kg, PO) in young healthy volunteers on their performance in visual paired associates learning (PAL) and delayed matching to sample (DMTS) visual short-term recognition memory tests. In the PAL test, clonidine 2 and guanfacine 29 mu g/kg improved the subjects' performance. In the DMTS test, clonidine at 5 mu g/kg delay-dependently impaired performance accuracy, and at 2 and 5 mu g/kg it also slowed responses. Guanfacine had no effect on DMTS test performance. Clonidine 5 and guanfacine 29 mu g/kg equally increased subjective feelings of sedation and reduced blood pressure. The results suggest that both clonidine and guanfacine facilitated PAL learning by improving "frontal strategies," but only clonidine disrupted "mnemonic processing" decreasing DMTS accuracy. The greater selectivity of guanfacine for alpha2A-adrenoceptor subtype may explain the different profile of action of the drugs. [Neuropsychopharmacology 20: 119-130, 1999] (C) 1998 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.