Altered responsiveness of central alpha 2-adrenoceptors in aging

The behavioural and ECoG spectrum power effects of clonidine, and yohimbine, an agonist and an antagonist at alpha 2-adrenoceptors, after their unilateral microinfusion into the rat locus coeruleus (LC) in young (50-70 days old) and old (13-15 months old) rats were studied. Clonidine (0.09, 0.19, 0.28 and 0.56 nmol) microinfused into the LC of young rats induced dose-dependent behavioural and ECoG slow wave sleep (SWS) with a significant increase in total voltage power and in the lower frequency bands. In contrast, yohimbine (1.3 and 2.6 nmol) infused into the LC of young rats produced ECoG desynchronization and a significant decrease in total voltage power. In contrast to young rats, clonidine (0.19 and 0.28 nmol) given into the LC did not affect behaviour and ECoG spectrum power in old rats. However, after higher doses of clonidine (0.56 and 1.2 nmol) a small and short-lasting period of behavioural and ECoG SWS was still evident. Similarly, in old rats yohimbine, at a dose (1.3 nmol) which was stimulatory in young animals, did not significantly affect behaviour and ECoG spectrum power. Higher doses of yohimbine (2.6 and 5.2 nmol) were required to induce behavioural and ECoG changes similar to those observed with lower doses of yohimbine in young rats. The present experiments suggest that there is a decreased responsiveness of LC alpha 2-adrenoceptors in old rats.