Treatment with the noradrenergic alpha-2 agonist clonidine, but not diazepam, improves spatial working memory in normal young rhesus monkeys.
Noradrenergic alpha-2 agonists such as clonidine and guanfacine improve working memory performance in aged monkeys. Guanfacine also improves cognition in young monkeys, but there are conflicting reports of the effects of clonidine in young adult human and nonhuman primates. In the present study, high doses of clonidine (0.02-0.1 mg/kg) significantly improved performance of the delayed response task, a test of spatial working memory, in young adult monkeys. Lower doses (0.0001-0.01 mg/kg), similar to those used in human studies (0.001-0.003 mg/kg), had no effect on task performance. In contrast, monkeys experimentally depleted of catecholamines by chronic reserpine treatment have been improved by both dose ranges. These results provide further support for the hypothesis that alpha-2 agonists improve cognition via actions at post-synaptic alpha-2 receptors, and suggest that conflicting results with clonidine in previous studies of prefrontal cortical function may result from insufficient dosage.
Franowicz
J S
JS
Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06520-8001, USA.
Arnsten
A F
AF
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D019329:Idazoxan / Q000494:pharmacology; D008253:Macaca mulatta; D008568:Memory / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013028:Space Perception / Q000187:drug effects
D018759:Adrenergic Uptake Inhibitors; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D006993:Hypnotics and Sedatives; D018341:Receptors, Adrenergic, alpha-2; D012110:Reserpine; D003000:Clonidine; D003975:Diazepam; D019329:Idazoxan