ABSTRACT
An overlapping distribution of alpha2-adrenergic receptors with cannabinoid receptors has been reported in certain brain structures such as the dorsal hippocampus. Thus, functional interactions between cannabinoid and alpha2-adrenergic systems in cognitive control seem possible. In the present study, we examine the possible role of alpha2-adrenergic receptors of the dorsal hippocampus on WIN55.212-2 state-dependent learning. 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. Post-training or pre-test intra-CA1 administration of the cannabinoid receptor agonist, WIN 55,212-2 [0.25 and 0.5microg/rat] induced amnesia. Amnesia produced by post-training WIN55,212-2 [0.5 microg/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 microg/rat] or yohimbine [0.5, 0.75, and 1 MQ/rat] did not affect memory retrieval per se. Pre-test intra-CA1 administration of clonidine [0.5 and 1 micro9/rat] or clonidine [0.25, 0.5, and 1 microg/rat] with an ineffective dose of WIN 55,212-2 [0.25 microg/rat] reversed post-training WIN55,212-2 [0.5 microg/rat,intra-CA1] induced memory impairment. Pre-test intra-CA1 microinjection of yohimbine [1 microg/rat] before administration of WIN55,212-2 [0.5 microg/rat, intra-CA1], however, dose-dependently inhibited WIN55.212-2 state-dependent memory. Modulation of a2-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]