asymmetric involvement of central and the peripheral nmda 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 n-methyl-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 intra-accumbens (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. morphine-dependence (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.