The amnesic effect of intra-central amygdala administration of a cannabinoid CB1 receptor agonist, WIN55,212-2, is mediated by a beta-1 noradrenergic system in rat

Abstract

In this study, we investigated effects of intra-central amygdala (intra-CeA) administrations of a cannabinoid agonist, WIN55,212-2 by itself and its interaction with β1-adrenoceptor agents on memory consolidation. We used a step-through inhibitory avoidance (IA) task to assess memory in male Wistar rats. The results showed that post-training intra-CeA administrations of different doses of WIN55,212-2 at doses of 0.1 and 0.25μg/rat impaired memory consolidation (or induced amnesia) as revealed by a decrease in step-through latency on the test day. Post-training intra-CeA injections of a β1-adrenoceptor agonist, isoprenaline (0.01, 0.025, 0.05μg/rat) by itself had no significant effect on memory consolidation, while at all doses prevented the amnesia induced by post-training injections of WIN55,212-2 (0.25μg/rat). Although, post-training intra-CeA administrations of β1-adrenoceptor antagonist, atenolol alone at different doses (0.01, 0.025, 0.05 and 0.1μg/rat) had no significant effect, but its co-administrations at doses of 0.05 and 0.1μg/rat along with an ineffective dose of WIN55,212-2 (0.05μg/rat) induced amnesia, and at dose of 0.1μg/rat along with an effective dose of WIN55,212-2 (0.25μg/rat) increased amnesia that induced by the later drug. Moreover, the improving effect of isoprenaline (0.025μg/rat) on amnesia induced by WIN55,212-2 (0.25μg/rat) was prevented by intra-CeA co-injections of atenolol at doses of 0.01 and 0.025μg/rat. The present results suggest that a β1-adrenoeceptor mechanism in the central amygdala (CeA) is involved in amnesia induced by post-training intra-CeA injections of WIN55,212-2.