MEDETOMIDINE, ATIPAMEZOLE, AND GUANFACINE IN DELAYED-RESPONSE PERFORMANCE OF AGED MONKEYS

The effects of a highly selective alpha-2 adrenergic agonist medetomid ine and its antagonist atipamezole were studied on the delayed respons e task performance of aged monkeys. Medetomidine, at the dose of 1.0 m u g/kg, improved the memory task performance, whereas atipamezole had no effect on the performance at any dose. It has earlier been shown th at alpha-2 adrenergic agonists clonidine and guanfacine improve age-as sociated memory impairment, but also contradictory effects of clonidin e have been reported. There is evidence that the ability of alpha-2 ag onists to improve DR task performance is due to its selective action o n the alpha-2A receptor subtype. Clonidine and medetomidine are much l ess selective than guanfacine with respect to alpha-2A and alpha-2B re ceptor subtypes. Therefore, we also studied the effect of guanfacine o n the memory task performance of the same aged monkeys in the same tes ting conditions to compare the effectiveness of these two alpha-2 adre nergic compounds. Guanfacine improved memory task performance at the d ose of 0.0001 mg/kg. The results indicate that alpha-2 agonists, indep endent of their different selectivity with respect to alpha-2A/2B rece ptor subtypes, are beneficial drugs in improving the performance in th e delayed response task. Copyright (C) 1996 Elsevier Science Inc.