Effects of α1- and α2-adrenoceptor agonist and antagonist in the dorsal hippocampus on cannabinoid state-dependent memory

Cannabinoids are a class of psychoactive compound that produce a wide range of effects in different number of species. The present study evaluated the possible role of α1- and α2-adrenergic receptors of the dorsal hippocampus on cannabinoid induced amnesia and cannabinoid state-dependent memory in adult male Wistar rats. The animals were bilaterally implanted with chronic cannulae in the CA1 regions of the dorsal hippocampus, trained in a step-down type inhibitory avoidance task, and tested 24h after training to measure step-down latency. Post-training intra-CA1 injection of cannabinoid receptors agonist, WIN55,212-2 (0.25 and 0.5 µg/rat) induced amnesia. Amnesia induced by post-training WIN55,212-2 (0.5 µg/rat) was restored by pre-test administration of the same dose of WIN55,212-2. Pre-test intra-CA1 injection of phenylephrine could not affect memory but clonidine improved memory impairment induced by WIN55,212-2. Furthermore, microinjection of phenylephrine or clonidine plus an ineffective dose of WIN55,212-2, synergistically restored amnesia induced by WIN55,212-2. On the other hand, pre-test intra CA1 microinjection of prazosin or yohimbine 2 min before WIN55,212- inhibited pre-test WIN55,212-2 response. These results indicate that α-adrenergic receptors of the dorsal hippocampal CA1 regions may play an important role in cannabinoid-induced amnesia and cannabinoid state-dependent memory.