Effects of medetomidine, an alpha-2 adrenoceptor agonist, and atipamezole, an alpha-2 antagonist, on spatial memory performance in adult and aged rats.

The effects of a novel, highly selective alpha-2 agonist, medetomidine, and its antagonist, atipamezole, were studied on the working memory of rats performing a spatial delayed alternation task. Testing was performed in two stages, at the age of 8.3 months (mean) and again when the rats were 17.6 months (mean). A low dose (3 micrograms/kg) and a high dose (30 micrograms/kg) of medetomidine improved the performance of the old rats in the memory task but had no effect on the young rats. The dose-response curve of medetomidine resembles that of guanfacine, another alpha-2 agonist. At the low dose of medetomidine (3 micrograms/kg) the animals showed no signs of sedation. Since medetomidine even at a low dose has a beneficial effect on the memory performance of old rats, it could be a good candidate for the treatment of age-associated memory dysfunction.