NMDA glutamate receptor inhibition in the dorsal hippocampus reduced the maintenance of electric foot shock stress -induced anxiety and depression like behaviors in mice

Introduction: In the present study, the effect of inhibition of glutamate NMDA receptors located in the dorsal hippocampus on the maintenance of anxiety and depression like behaviors induced by electric foot shock stress was investigated. Materials and Methods: NMARI male mice were divided into two categories. The first category received electro foot shock for 30 minutes after injection of memantine (1, 5 and 10 mg/kg) or saline (1ml/kg) intraperitoneally. The second category was bilaterally cannulated in the dorsal hippocampus and one week later, the animals first received different doses of memantine (1, 5 and 10 μg /mouse) intra-hippocampally and five min before stress. Remarkably, this procedure was repeated for 4 consecutive days. Six days after stress termination, maintenance of anxiety in animals was examined using the elevated plus maze. Two days after the anxiety test, forced swimming test was conducted for depression like behavior maintenance evaluation. Results: Stress reduced the open arm time in the elevated plus maze. Intraperitoneal administration of memantine prevented the stress effect. Also, intra-dorsal hippocampus administration of memantine preventd the maintenance of anxiety induced by stress. Stress also increased the immobility time in the forced swimming test. Both intraperitoneal and intra-dorsal hippocampus administration of memantine inhibited the maintenance of depression induced by stress. Conclusion: Electric foot shock can lead to persistence anxiety and depression like behavior in mice. Inhibition of NMDA glutamate receptors in the dorsal hippocampus reduced the stress response.