Involvement of dorsal hippocampal NMDA-glutamatergic system in anxiety-related behaviors of rats

Dorsal hippocampus is one of the brain regions which plays an important role in anxiety. In the present study we investigated the effects of Intra-dorsal hippocampus (CA1) microinjection of NMDA-glutamatergic receptor agonist, NMDA and its antagonist, MK-801 on anxiety-related behavior in rats. Elevated plus-maze (EPM) which is one of the common methods employed for testing of anxiety was used in this study. Rats were anaesthetized with a mixture of ketamine and xylazine and special cannulas were inserted stereotaxically into the CA1 region of the dorsal hippocampus. After a one-week recovery, the effects of intra-CA1 administration of NMDA receptor agents were studied. Bilateral Intra-dorsal hippocampus microinjection of different doses of NMDA (0.25, 0.5, 0.75 and 1 μg/rat) increased the percentage of open arm time (%OAT) and open arm entries (%OAE), indicating an anxiolytic-like behavior. On the other hand, administration of MK-801 (60, 125, 250 and 500 ng/rat) decreased %OAT and %OAE significantly. Pre-treatment administration of MK-801(60, 125, 250 and 500 ng/rat) reversed the anxiolytic effect of NMDA (0.5 μg/rat) microinjection into the dorsal hippocampus in a dose-dependent manner. From the findings of the present study, it can be concluded that the NMDA-glutamatergic system in the dorsal hippocampus is involved in anxiety-related behaviors.