The role of alpha-adrenoceptors in the amnestic effect of intracerebroventricular dexamethasone.

Corticosteroids exert dual enhancing or impairing effects on cognitive functions. While their memory-enhancing effects have been well investigated, the mechanisms involved in their amnestic effects are not completely understood. Thus, we examined the role of alpha-adrenoceptors on dexamethasone-induced amnesia using step-through passive avoidance test in rat. Intracerebroventricular (i.c.v.) injection of dexamethasone (5 and 10 microg per rat) decreased the retention latencies. Likewise, intraperitoneal administration of alpha(2)-adrenoceptor agonist clonidine (0.1-0.3 mg kg(-1)) but not alpha(2)-adrenoceptor antagonist yohimbine (0.5-2 mg kg(-1)) decreased the retention latency. Yohimbine pre-treatment decreased the amnestic effects of dexamethasone or dexamethasone plus clonidine. On the other hand, intraperitoneal administration of alpha(1)-adrenoceptor agonist phenylephrine (0.5-2 mg kg(-1)) per se increased, while prazosin at 2 mg kg(-1) decreased the retention latency. Administration of phenylephrine before dexamethasone completely reversed the amnestic effect of the latter, while prozosin did not affect dexamethasone-induced amnesia. These data suggest that dexamethasone may induce its amnestic effect through activation of alpha(2)-adrenoceptors, leading to decreased alpha(1)-adrenergic activity.