Involvement of ventral tegmental area muscarinic and NMDA receptors on memory retrieval in passive avoidance task

Behavioural studies have suggested interactions between cholinergic and glutamatergic systems. In the present study, the effect of intra-VTA pretest administration of a nonselective muscarinic acetylcholine antagonist, scopolamine, glutamatergic drugs and their interaction on inhibitory avoidance response was investigated.Rats were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine and then placed in a stereotaxic apparatus. Also, two stainless-steel cannuale were placed in the ventral tegmental area. A step-through inhibitory avoidance task was used for memory assessment in male Wistar rats. The drug injected 5 min before testing and the step-through latency was measured with a stopwatch as inhibitory avoidance memory.The results showed that intra-VTA pretest administration of scopolamine (3 and 4 μg/rat) and NMDA receptor antagonist, MK-801 (1 and 2 μg/rat) impair memory retention. Interestingly, co-administration of an ineffective dose of MK801 (0.5 μg/rat) with ineffective doses of scopolamine (1 and 2 μg/rat) significantly decreased the inhibitory avoidance memory. Although pretest intra-VTA injections of NMDA (0.001 and 0.01 μg/rat) had no effect by itself,but its co-administration with scopolamine (4 μg/rat) prevented the decreasing effect of scopolamine on inhibitory avoidance memory retention.Our data may indicate that muscarinic and NMDA receptors in the VTA may be involved in the mechanism(s) modulating inhibitory avoidance memory retention through the VTA dopaminergic projections.