Effects of cholinergic system of dorsal hippocampus of rats on MK-801 induced anxiolytic-like behavior

Rationale: Some investigations have shown that the glutamate receptors play a critical role in cognitive processes such as learning and anxiety. Objectives: The possible involvement of the cholinergic system of the dorsal hippocampus in the anxiolytic-like response induced by MK-801, NMDA receptor antagonist, was investigated in the present study. Methods: Male Wistar rats were used in the elevated plus maze apparatus to test the parameters: open arm time (%OAT), open arm entries (%OAE), close arm time (%CAT), close arm entries (%CAE) and other exploratory behaviors (locomotor activity, grooming, rearing and defecation) of anxiety-like response. Results: The data indicated that intra-CA1 administration of MK-801 increased %OAT (2 μg/rat) and %OAE (1 and 2 μg/rat) while decreased %CAT and %CAE and did not alter other exploratory behaviors, indicating an anxiolytic-like effect. Moreover, intra-hippocampal injections of mecamylamine, a cholinergic receptor antagonists (2 μg/rat) and scopolamine (4 μg/rat), by themselves, 5 min before testing, increased %OAT and %OAE but decreased %CAT and %CAE and did not alter locomotor activity and other exploratory behaviors, suggesting an anxiolytic-like effect. On the other hand, intra-CA1 co-administration of an ineffective dose of scopolamine (3 μg/rat), but not mecamylamine (1 μg/rat), with an ineffective dose of MK-801 (0.5 μg/rat) increased %OAT and %OAE and decreased %CAT and %CAE. The data may indicate the possible involvement of the cholinergic system of the CA1 in the anxiolytic-like response induced by MK-801.

► Intra-CA1 injection of MK-801 induced anxiolytic-like behaviors. ► Intra-CA1 injection of mecamylamine and scopolamine induced anxiolytic-like behaviors. ► Intra-CA1 co-injection of scopolamine increased anxiolytic-like behaviors by MK-801. ► Intra-CA1 co-administration of mecamylamine did not alter behaviors-induced by MK-801.