Medetomidine, atipamezole, and guanfacine in delayed response performance of aged monkeys.

The effects of a highly selective alpha-2 adrenergic agonist medetomidine and its antagonist atipamezole were studied on the delayed response task performance of aged monkeys. Medetomidine, at the dose of 1.0 micrograms/kg, improved the memory task performance, whereas atipamezole had no effect on the performance at any dose. It has earlier been shown that alpha-2 adrenergic agonists clonidine and guanfacine improve age-associated memory impairment, but also contradictory effects of clonidine have been reported. There is evidence that the ability of alpha-2 agonists to improve DR task performance is due to its selective action on the alpha-2A receptor subtype. Clonidine and medetomidine are much less selective than guanfacine with respect to alpha-2A and alpha-2B receptor subtypes. Therefore, we also studied the effect of guanfacine on the memory task performance of the same aged monkeys in the same testing conditions to compare the effectiveness of these two alpha-2 adrenergic compounds. Guanfacine improved memory task performance at the dose of 0.0001 mg/kg. The results indicate that alpha-2 agonists, independent of their different selectivity with respect to alpha-2A/2B receptor subtypes, are beneficial drugs in improving the performance in the delayed response task.