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.
Wang
Min
M
Laboratory of Higher Brain Functions, Institute of Neurobiology, Fudan University, Shanghai 200433, The People's Republic of China.
Ji
Jin-Zhao
JZ
Li
Bao-Ming
BM
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001245:Association Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016316:Guanfacine / Q000494:pharmacology*; D019329:Idazoxan / Q000494:pharmacology; D008253:Macaca mulatta; D010775:Photic Stimulation; D011597:Psychomotor Performance / Q000187:drug effects*; D018709:Statistics, Nonparametric
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D016316:Guanfacine; D019329:Idazoxan