Academy of Medical Sciences of I.R. Iran Archives of Iranian Medicine 1029-2977 14 6 2011 11 01 Modulation of WIN55,212-2 State-Dependent Memory by α2-Adrenergic Receptors of the Dorsal Hippocampus 389 395 EN Morteza Piri Mohammad-Reza Zarrindast Journal Article BACKGROUND: An overlapping distribution of α2-adrenergic receptors with cannabinoid receptors has been reported in certain brain structures such as the dorsal hippocampus. Thus, functional interactions between cannabinoid and α2-adrenergic systems in cognitive control seem possible. In the present study, we examine the possible role of α2-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 0.5µg/rat) induced amnesia. Amnesia produced by post-training WIN55,212-2 (0.5 µg/rat) was reversed by pre-test administration of WIN55,212-2, that was due to a state-dependent effect. Pre-test intra-CA1 microinjections of clonidine (0.25, 0.5 and 1 μg/rat) or yohimbine (0.5, 0.75, and 1 μg/rat) did not affect memory retrieval per se. Pre-test intra-CA1 administration of clonidine (0.5 and 1 μg/rat) or clonidine (0.25, 0.5, and 1 μg/rat) with an ineffective dose of WIN 55,212-2 (0.25 µg/rat) reversed post-training WIN55,212-2 (0.5 µg/rat,intra-CA1) induced memory impairment. Pre-test intra-CA1 microinjection of yohimbine (1 μg/rat) before administration of WIN55,212-2 (0.5 µg/rat, intra-CA1), however, dose-dependently inhibited WIN55,212-2 state-dependent memory. CONCLUSION: Modulation of α2-adrenergic receptors in the dorsal hippocampal 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).