Scopolamine induced memory impairment; possible involvement of NMDA receptor mechanisms of dorsal hippocampus and/or septum

Background and aimThe anatomical connections of septum and hippocampus and the influence of cholinergic and glutamatergic projections in these sites have been reported. In the present study, the effect of pre-training intra-dorsal hippocampal (CA1) and intra-medial septal (MS) administration of scopolamine, a nonselective muscarinic acetylcholine antagonist, and NMDA receptor agents and their interactions, on acquisition of memory have been investigated.MethodsThe animals were bilaterally implanted with chronic cannulae in the CA1 regions and in the medial septum. Animals were trained in a step-through type inhibitory avoidance task, and tested 24 h after training to measure step-through latency as memory retrieval.ResultsIntra-CA1 or intra-MS injections of scopolamine (0.5, 1 and 2 μg/rat) and D-AP7 (a competitive NMDA receptor antagonist; 0.025, 0.05 and 0.1 μg/rat) reduced, while NMDA (0.125 and 0.25 μg/rat) increased memory. Intra-MS injection of a subthreshold dose of NMDA reduced scopolamine induced amnesia in the MS. However, similar injection of NMDA into CA1 did not alter scopolamine response when injected into CA1. Moreover, intra-MS or -CA1 injection of a subthreshold dose of NMDA did not alter scopolamine response in the CA1 or MS respectively. On the other hand, co-administration subthreshold doses of D-AP7 and scopolamine into CA1 and/or MS induced amnesia.ConclusionsThe cholinergic system between septum and CA1 are modulating memory acquisition processes induced by glutamatergic system in the CA1 or septum and co-activation of these systems in these sites can influence learning and memory.

► Intra-CA1 or septum infusion of SCO and D-AP7 decreased while NMDA increased memory.
► NMDA did not alter but D-AP7 increased SCO-induced amnesia in the CA1.
► NMDA decreased but D-AP7 increased SCO-induced amnesia in the septum.
► NMDA in the CA1 did not alter SCO-induced amnesia in septum and vice versa.
► D-AP7 in CA1 or septum increased the response of SCO in each site.