Guanfacine and clonidine, alpha 2-agonists, improve paired associates learning, but not delayed matching to sample, in humans

The present study compares the effects of two alpha 2-agonists, clonidine (0.5, 2, and 5 micrograms/kg, p.o.) and guanfacine (7 and 29 micrograms/kg, p.o.) 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 micrograms/kg improved the subjects' performance. In the DMTS test, clonidine at 5 micrograms/kg delay-dependently impaired performance accuracy, and at 2 and 5 micrograms/kg it also slowed responses. Guanfacine had no effect on DMTS test performance. Clonidine 5 and guanfacine 29 micrograms/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 "mneomonic processing" decreasing DMTS accuracy. The greater selectivity of guanfacine for alpha 2A-adrenoceptor subtype may explain the different profile of action of the drugs.