Modulation of WIN55,212-2 State-Dependent Memory by (alpha)2- Adrenergic Receptors of the Dorsal Hippocampus

Background: An overlapping distribution of (alpha)2-adrenergic receptors with cannabinoid receptors has been reported in certain brain structures such as the dorsal hippocampus. Thus, functional interactions between cannabinoid and (alpha)2-adrenergic systems in cognitive control seem possible. In the present study, we examine the possible role of (alpha)2-adrenergic receptors of the dorsal hippocampus on WIN55,212-2 state-dependent learning. Methods: Adult male Wistar rats were bilaterally implanted with chronic cannulae in the CA1 regions of their dorsal hippocampi trained in a step-down type inhibitory avoidance task and tested 24 hr after training, to measure step-down latency. Results: Post-training or pre-test intra-CA1 administration of the cannabinoid receptor agonist, WIN 55,212-2 (0.25 and 0.5(mu)g/rat) induced amnesia. Amnesia produced by post-training WIN55,212-2 (0.5 (mu)g/rat) was reversed by pre-test administration of WIN55,212-2, that was due to a state-dependent effect. Pre-test intra-CA1 microi njections of clonidine (0.25, 0.5 and 1 (mu)g/rat) or yohimbine (0.5, 0.75, and 1 (mu)g/rat) did not affect memory retrieval per se. Pre-test intra-CA1 administration of clonidine (0.5 and 1 (mu)g/rat) or clonidine (0.25, 0.5, and 1 (mu)g/rat) with an ineffective dose of WIN 55,212-2 (0.25 (mu)g/rat) reversed post-training WIN55,212-2 (0.5 (mu)g/rat,intra-CA1) induced memory impairment. Pre-test intra-CA1 microinjection of yohimbine (1 (mu)g/rat) before administration of WIN55,212-2 (0.5 (mu)g/rat, intra-CA1), however, dosedependently inhibited WIN55,212-2 state-dependent memory. Conclusion: Modulation of (alpha)2-adrenergic receptors in the dorsal hip pocampal CA1 regions can influence WIN55,212-2 induced amnesia and WIN55,212-2 state-dependent learning of an inhibitory avoidance task by pre- or post-synaptic mechanism(s).