Effects of Memantine, an NMDA Antagonist, on Metabolic Syndromes in Female NMRI Mice

Introduction: The brain glutamate neurotransmitter system and its NMDA receptors in the nucleus accumbens play an important role in the incidence of the phenomena 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 cannula placement in the nucleus accumbens, one group of the animals received different intra-accumbens doses of memantine (0.1, 0.5 and 1 µg/mouse) 5 minutes before receiving the electric shock stress at their soles (using a Communication Box) and the other group received intraperitoneal doses of memantine (0.1, 0.5 and 1mg/kg) 30 minutes before receiving the same shock. Chronic stress increased the animals' plasma corticosterone, food and water intake and weight and 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 and water and food intake, or else 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, with gender playing a significant role in producing this effect.