THE ROLE OF α-ADRENOCEPTORS IN THE AMNESTIC EFFECT OF INTRACEREBROVENTRICULAR DEXAMETHASONE

Abstract

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 α-adrenoceptors on dexamethasone-induced amnesia using step-through passive avoidance test in rat. Intracerebroventricular (i.c.v.) injection of dexamethasone (5 and 10 μg per rat) decreased the retention latencies. Likewise, intraperitoneal administration of α 2-adrenoceptor agonist clonidine (0.1–0.3 mg kg −1) but not α 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 α 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 α 2-adrenoceptors, leading to decreased α 1-adrenergic activity.