Reserpine impairs spatial working memory performance in monkeys: reversal by the alpha 2-adrenergic agonist clonidine.
Repeated daily treatment with the catecholamine-depleting agent, reserpine, dramatically reduced performance on the delayed response task, a test of spatial working memory that depends upon the integrity of the prefrontal cortex. Delayed response performance fell from an average of 27.2/30 trials correct before reserpine treatment to an average of 20.4/30 trials correct after repeated reserpine administration. Injection of the alpha 2-adrenergic agonist, clonidine (0.0001-0.05 mg/kg), to chronic reserpine-treated monkeys significantly restored performance on the delayed response task; performance after an optimal dose averaged 27.8/30 trials correct. Clonidine's beneficial effects on delayed response performance were longlasting; monkeys remained improved for more than 24 h after a single clonidine injection. The finding that clonidine is efficacious in reserpinized animals supports the hypothesis that alpha 2-adrenergic agonists improve cognitive function through actions at postsynaptic, alpha 2-adrenergic receptors on non-adrenergic cells. In contrast to the delayed response task, reserpine had little effect on performance of a visual discrimination task, a reference memory task which does not depend on the prefrontal cortex. These results emphasize the importance of postsynaptic, alpha 2-adrenergic mechanisms in the regulation of working memory.
Cai
J X
JX
Kunming Institute of Zoology, Academia Sinica, Yunnan, China.
Ma
Y Y
YY
Xu
L
L
Hu
X T
XT
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D009638:Norepinephrine / Q000502:physiology; D012110:Reserpine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012193:Reversal Learning / Q000187:drug effects; D013028:Space Perception / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D006993:Hypnotics and Sedatives; D012110:Reserpine; D003000:Clonidine; D009638:Norepinephrine