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Introduction: The brain glutamate system plays a central role in response to stress. This study examines the effect of memantine (a NMDA glutamate receptor antagonist) on stress from plantar electrical shock in male NMRI mice (Pasture Institute, Iran), weighing 25-30 g (n=6/group). Methods: The nucleus accumbens was bilaterally cannulated in a group of animals, and seven days later, different doses of memantine (1 and 5 μg/mouse) was administered 5 min before inducing stress. In other groups, different doses of the drug (1 and 5 mg/kg) were administered to the animals intraperitoneally 30 min before the stress induction. Then food and water intake, anorexia, and the amount of urine and fecal materials were measured. Results: The stress reduced food intake and increased water intake in the animals. In addition, anorexia, fecal weight and urine volume were increased dramatically in these animals. Intraperitoneal memantine injection increased food intake and decreased water intake. This occurred when the drug was administered intra-accumbally, too. Memantine inhibited stress-induced anorexia when administered either intraperitoneally or intra-accumbally. Memantine (both peripherally and centrally) also changed stress-induced fecal passage but decreased urination. Conclusion: Memantine administration can inhibit or potentiate stress effects, which may be at least partially integrated in the nucleus accumbens. [ABSTRACT FROM AUTHOR]