Inhibitory avoidance memory deficit induced by scopolamine: Interaction of cholinergic and glutamatergic systems in the ventral tegmental area

Interaction of cholinergic and glutamatergic inputs in the ventral tegmental area (VTA) influencing a learned behavior is a topic of great interest. In the present study the effect of intra-VTA administration of a nonselective muscarinic acetylcholine antagonist, scopolamine, and N-methyl-d-aspartate (NMDA) receptor agents by themselves as well as their interactions on consolidation and retrieval of inhibitory avoidance (IA) memory have been investigated. A step-through inhibitory avoidance task was used for memory assessment in male Wistar rats. The results showed that intra-VTA administration of scopolamine (1 and 2 μg/rat) and NMDA receptor antagonist, MK-801 (0.75 and 1 μg/rat) immediately after training, impaired consolidation of IA memory. Interestingly, co-administration of an ineffective dose of MK-801 (0.5 μg/rat) with ineffective doses of scopolamine (0.25 and 0.5 μg/rat) significantly decreased the consolidation process. Post-training intra-VTA injections of NMDA (0.001 and 0.01 μg/rat) had no effects by itself, whereas its co-administration with scopolamine (2 μg/rat) prevented the effect of the later drug. The results also showed that pre-test intra-VTA administration of scopolamine (3 and 4 μg/rat) and MK-801 (1 and 2 μg/rat) impaired retrieval of the IA memory. Moreover, co-administration of an ineffective dose of MK-801 (0.5 μg/rat) with ineffective doses of scopolamine (1 and 2 μg/rat) increasingly reduced the retrieval of the IA memory. On the contrary to its post-training treatment, pre-test administration of NMDA either alone or in combination with scopolamine caused no significant effect on retrieval of IA memory. It can be concluded that muscarinic acetylcholine and NMDA glutamate receptors in the VTA are involved in the mechanism(s) underlying consolidation and retrieval of the IA memory.