Effects of memantine, an NMDA antagonist, on metabolic syndromes in female NMRI mice

Introduction: The brain glutamate neurotransmitter system and its NMDA [N-methyl D-aspartate] receptors in the nucleus accumbens play an important role in the incidence of sensitivity and addiction. The present study examined the inhibitory effect of glutamate NMDA receptors in the nucleus accumbens in response to chronic stress

Methods: After the unilateral and bilateral placement of cannula[e] in the nucleus accumbens, one group of the animals received different doses of intra-accumbens memantine [0.1, 0.5 and 1 micro g per mouse] 5 minutes before receiving the electric shock stress at their soles [using a Communication Box] and the other group received intraperitoneal memantine [doses of 0.1, 0.5 and 1mg per kg] 30 minutes before receiving the same shock. Chronic stress increased the animals' weight, plasma corticosterone, food and water intake, but reduced their defecation rates and eating latency

Results: The intraperitoneal administration of memantine increased plasma corticosterone, water intake, fecal weight, and eating latency, but had no effect on food intake or weight. The dose and site-dependent intra-accumbens administration of memantine either exacerbated the effects of stress on plasma corticosterone levels, water and food intake, or had no effect on these parameters. Furthermore, the administration of memantine had no effect on animal's weight and inhibited the effects of stress on fecal weight and eating latency

Discussion: The inhibition of glutamate NMDA receptors in the nucleus accumbens can inhibit and/or exacerbate the dose and site-dependent effects of chronic stress, and gender plays a significant role in producing this effect too

[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]

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. 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 micro g/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. 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. 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