Asymmetric Involvement of Central and the Periphera lNMDA Glutamate Receptors in the Expression of Withdrawal Syndrome in Morphine-Dependent Mice

Introduction: morphine withdrawal syndrome is mediated via several central and peripheral neurological pathways. in the present study we investigated the role of nmethyl- d aspartic acid (nmda) glutamate receptor on naloxone-induced withdrawal syndrome in morphine-conditioned mice. materials and methods: we designed two separate experiments. in experiment one, 30 male nmri mice were divided into 5 groups, pretreated with memantine (0.1, 1 and 5 mg/kg; i.p.) followed by morphine-dependence period for 3 days. in the other experiment, 48 male nmri mice distributed into 8 groups, pretreated with intraaccumbens (iac) memantine (1 and 5 μg/animal) within the right, left and both side of nucleus accumbens (rnacc, lnacc and bnacc) followed by i.p. morphinedependence (3 days). on day 4, in both experiments, morphine was injected into mice, followed by naloxone. then naloxone-induced total jumping count, jump height and defecation in morphine-conditioned mice were recorded for 30 min. results: pre-treatment by i.p. injection of memantine significantly attenuated naloxone precipitated jumping count/30 min, jumping height (mm) and fecal material output in morphine dependent mice (p<0.05). also, iac pretreatment with memantine in lnacc, rnacc and bnacc significantly declined the effect of i.p. injection of naloxone on total jumping count and jumping height (p<0.05), pretreatment within memantine in lnacc, rnacc and bnacc had no effect on defecation (p>0.05). conclusion: these findings indicated asymmetric involvement of central and peripheral nmda glutamate receptors in withdrawal syndrome development in morphine-dependent mice.