Introduction: Similarities in the memory impairment between Alzheimer patients and scopolamine treated animals have been reported. In the present study, the possible role of α-adrenergic receptors of the dorsal hippocampus on scopolamine state-dependent memory in adult male Wistar rats was evaluated. Methods: The animals were bilaterally implanted with chronic cannulae in the CA1 regions of the dorsal hippocampus, trained in a step-through type inhibitory avoidance task, and tested 24 h after training to measure step-through latency. Results: Post-training intra-CA1 administration of scopolamine (0.5 and 2μg/rat) dose-dependently reduced the step-through latency, showing an amnestic response. Amnesia produced by post-training scopolamine (2 μg/rat) was reversed by pre-test administration of the scopolamine (0.5 and 2 μg/rat) that is due to a state-dependent effect. Pre-test intra-CA1 injection of α1-adrenoceptor agonist, phenylephrine (0.25, 0.5 μg/rat) in the dose range that we used, could not affect memory impairment induced by post-training injection of scopolamine (2 μg/rat). However intra-CA1 pretest injection of α2-adrenoceptor agonist, clonidine (0.5 μg/rat) improved post-training scopolamine (2 μg/rat) intra-CA1 injection induced retrieval impairment. Furthermore, pre-test intra-CA1 microinjection of phenylephrine (0.25 and 0.5 μg/rat) or clonidine (0.25 and 0.5 μg/rat) with an ineffective dose of scopolamine (0.25 μg/rat), synergistically improved memory performance impaired by post-training scopolamine (2 μg/rat). Our results also showed that, pre-test injection of α1-receptor antagonist prazosin (1, 2 μg/rat) or α2-receptors antagonist yohimbine (1, 2 μg/rat) before effective dose of scopolamine (2 μg/rat) prevented the improvement of memory by pre-test scopolamine. Conclusion: These results suggest that α1- and α2-adrenergic receptors of the dorsal hippocampal CA1 region may play an important role in scopolamine-induced amnesia and scopolamine state-dependent memory
