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.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000647:Amnesia / Q000139:chemically induced*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D008568:Memory / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015016:Yohimbine; D003907:Dexamethasone; D003000:Clonidine; D011224:Prazosin