Anxiogenic and anxiolytic effects of memantine injected into the ventral hippocampus in male stressed mice.

Abstract

The effects of intra-ventral hippocampal memantine administration in male NMRI stressed mice were studied. Two stainless steel gauge 23 guide cannulas were placed in the middle part of the mice ventral hippocampus using stereotaxic coordination. Seven days later, the animals were undergone to the stress protocol as follows: They experience four consecutive electro-foot shock stress sessions lasting for 10min. Five or 30min before each stress session, the animals received intra-ventral hippocampal (0.1, 1 and, 5µg/mouse) or intraperitoneal (1,5, and 10mg/kg) memantine respectively. Eight days after stress termination, the animals were tested either for the maintenance of either anxiety (elevated plus maze) or depression (forced swimming test). Animals show anxiety eight days after stress termination. Intra-ventral hippocampal infusion of memantine (5µg/mouse) 5min before stress inhibited the anxiety-like behaviors. However, other doses of the drug exacerbate the stress effect. The drug, when injected peripherally exacerbated the stress effect in all doses. The drug by itself had no effect. In addition, animals also show depression nine days after stress termination and memantine (0.1, 1, and 5µg/mouse) reduced the stress effect. The drug (0.1µg/mouse) by itself induced depression in the animals. However, the drug when injected peripherally reduced the stress effect in all doses. It could be concluded that NMDA glutamate receptors in the ventral hippocampus may play a pivotal role in the mediation of maintenance of anxiety and depression induced by stress in the mice.