Involvement of dorsal hippocampal α-adrenergic receptors in the effect of scopolamine on memory retrieval in inhibitory avoidance task

The present study evaluated the possible role of alpha-adrenergic receptors of the dorsal hippocampus on scopolamine-induced amnesia and scopolamine 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-through type inhibitory avoidance task, and tested 24 h after training to measure step-through latency. Results indicate that post-training or pre-test intra-CA1 administration of scopolamine (1 and 21 mu g/rat) dose-dependently reduced the step-through latency, showing an amnestic response. Amnesia produced by post-training scopolamine (2 mu g/rat) was reversed by pre-test administration of the scopolamine that is due to a state-dependent effect. Interestingly, pre-test intra-CA1 microinjection of alpha 1-adrenergic agonist, phenylephrine (1 and 2 mu g/rat) or alpha 2-adrenergic agonist, clonidine improved post-training scopolamine (2 mu g/rat)-induced retrieval impairment. Furthermore, pre-test intra-CA1 microinjection of phenylephrine (0.25, 0.5 and 1 mu g/rat) or clonidine (0.25, 0.5 and 1 mu g/rat) with an ineffective dose of scopolamine (0.25 mu g/rat), synergistically improved memory performance impaired by post-training scopolamine. On the other hand, pre-test injection of alpha 1-receptors antagonist prazosin (1 and 2 mu g/rat) or alpha 2-receptors antagonist yohimbine (1 and 2 mu g/rat) prevented the restoration of memory by pre-test scopolamine. It is important to note that pre-test intra-CA1 administration of the same doses of prazosin or yohimbine, alone did not affect memory retrieval. These results suggest that alpha 1- and alpha 2-adrenergic receptors of the dorsal hippocampal CA1 regions may play an important role in scopolamine-induced amnesia and scopolamine state-dependent memory. (C) 2010 Elsevier Inc. All rights reserved.