Effect of Memantine Administration within the Nucleus Accumbens on Changes in Weight and Volume of the Brain and Adrenal Gland during Chronic Stress in Female Mice

Objective: In the present study, we examined the effects of memantine administration within the nucleus accumbens on the alterations in brain and adrenal volumes and weight ratios induced by stress from electric foot shock. Methods: A group of mice received various doses of memantine (0.1, 0.5 and 1 mg/kg) prior to induction of stress. Another group underwent intra-accumbal cannulation after anesthesia. One week later, memantine (0.1, 0.5 and 1 µg/mouse) was injected within the nucleus accumbens prior to induction of stress. Subsequently all animals were killed. Their brains and adrenal glands were removed and fixed in 4% formalin. The volume and weight was determined by mercury immersion and method respectively. Results: The stress group showed evidence of reduction in brain volume and weight ratio to volume, and weight of the adrenal gland. Memantine increased the ratio of the brain volume and weight to the volume and weight of the adrenal gland. Memantine administration within the nucleus accumbens also could alter this ratio. Hence, all three doses of memantine that were injected on the right side and bilateral to the nucleus inhibited the effects of stress. Conclusion: Inhibition of NMDA receptors in the nucleus accumbens can inhibit the destructive effects of chronic stress on brain volume and weight. In addition, memantine can inhibit the influence of stress on adrenal volume and weight. We have shown that this effect was both dose and injection site dependent. In this regard, the left side of the nucleus was weaker.