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

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.
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.
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 (P0.05). These findings indicated asymmetric involvement of central and peripheral NMDA glutamate receptors in withdrawal syndrome development in morphine-dependent mice.