Dopaminergic system in CA1 modulates MK-801 induced anxiolytic-like responses

Abstract

Rationale: Today, there is relatively no debate on the notion that NMDA receptor antagonist agents in the hippocampus induce anxiolytic-like effects through distinct mechanisms. There is also a bulk of studies showing the involvement of the dopaminergic system in NMDA induced behaviors. Thus, on the basis of the involvement of dopaminergic system in anxiety-related behaviors, the present study aimed to investigate the involvement of the dorsal hippocampal (CA1) dopaminergic system in anxiolytic-like responses induced by MK801 (NMDA receptor antagonist) in male Wistar rats.

Methods: We used the elevated plus maze to test anxiety. This apparatus has widely been employed to test parameters of anxiety-related behaviors including the open arm time percentage (%OAT), open arm entries percentage (%OAE), locomotor activity, grooming (the rat rubs its face), rearing (the rat maintains an erect posture) and defecation (the number of boli defection).

Results: The data showed that, intra-CA1 injection of MK801 (2 μg/rat) increases %OAT and %OAE but not other exploratory behaviors, indicating an anxiolytic-like effect. Moreover, sole intra-CA1 injection of SCH23390, dopamine D1 receptor antagonist, (0.25, 0.5 and 1 μg/rat) and sulpiride, dopamine D2 receptor antagonist, (0.25,0.5 and 0.75 μg/rat) did not alter anxiety-like behaviors. Co-administration of subthreshold doses of SCH23390 (0.5 μg/rat) and MK801 (0.5 g/rat), induced anxiolytic-like behaviors. Furthermore, intra-CA1 administration of different doses of sulpiride (0.12, 0.5 and 0.75 μg/rat), 5 min before the injection of an effective dose of MK801 (2 μg/rat), decreased %OAT and %OAE, however did not alter other exploratory behaviors induced by MK801.

Conclusion: Our results suggested a modulatory effect of the CA1 dopaminergic system on the anxiolytic-like effects induced by MK801.