The alpha(2A)-adrenergic agonist guanfacine improves visuomotor associative learning in monkeys.

Two monkeys were trained on two-problem visuomotor associations: if the cue was a circle pattern, move a handle to the left ('go-left'), and if it was a triangle pattern, move the handle to the right ('go-right'). These two visuomotor associations were unchanged throughout all the experiments and therefore were very familiar to the monkeys. For learning of new visuomotor associations, each monkey was presented with a new set of four novel patterns in each and every daily session, two of which instructed 'go-left' response and the other two 'go-right' response. Systemically administered guanfacine, a selective alpha(2A)-adrenergic agonist, improved the monkeys' learning ability: trials and errors to the learning criterion of 90% correct decreased significantly. The monkeys showed an enhanced capability of using at least three response strategies: win-stay on 'repeat trial', change-stay and change-shift on 'change trial'. The beneficial effect could be reversed by the coadministered idaxozan, an alpha(2)-adrenergic antagonist, which had no effect when administered alone. Similar treatment with guanfacine had no beneficial effect on visual discriminative learning, a task that involves the inferotemporal cortex. The present results indicate that stimulation by guanfacine of alpha(2A)-adrenoceptors improves visuomotor associative learning, probably through actions at alpha(2A)-adrenoceptors in the prefrontal cortex.