Gene Expression And Synaptic Interface Structure In Specific Brain Regions Of Morphine Dependent Rats And Related Influences Of Dizocilpine

Objective: To explore the role of NMDA receptors in both opiate physical and psychological dependence by investigating the effects of dizocilpine (MK-801) on morphine-induced conditioned place preference (CPP) and spontaneous withdrawal signs in SD rats.Methods Fifty-one male Sprague-Dawley rats were randomly assigned to morphine, dizocilpine intervention and saline control groups. Rats of the morphine group were injected i.p. with morphine twice a day for 10 days in ascending schedule. Rats of the intervention group were injected i.p. with dizocilpine (0.075 mg/kg) 30 minutes before morphine injections (identical to the morphine group). Rats of the control group were treated by saline according to control principle. Conditioned place preference (non-preferred compartment in white chamber) was observed at day 5 and 9 during the treatment, day 1, 3 and 6 after the treatment. Withdrawal signs, including teeth chattering (TC), wet dog shakes (WS), rearing, stretching, penis licking (PL), ptosis, pilo-erection (PE), diarrhea, and weight loss (WL) were recorded at day 1, 3 and 6 after the treatment. Data were analyzed using one-way ANOVA, followed by LSD.Results (1) There were no differences in the time for rats staying in white chamber among three groups before the treatment (P>0.05). The time was significantly longer in morphine group than in control group at day 5, day 9 during the treatment, day 1, day 3 after the treatment (P< 0.01, P<0.01, P<0.05, P<0.05, respectively). However there was no statistically significant difference between intervention group and control group at all the time-points. The time was significantly shorter in intervention group than in morphine group at day 5, day 9 during the treatment (P<0.01). (2) The scores of total withdrawal signs, WL, TC, and WS, at day 1, day 3 after the treatment, were significantly higher in morphine group than in control group, but significantly lower inintervention group than in morphine group. No statistically significant difference was found between intervention group and control group.Conclusions (1) The chronic morphine treatment developed conditioned place preference, and co-administration of dizocilpine with morphine inhibited the morphine-induced CPP. (2) Rats ofin morphine group expressed marked withdrawal signs, and dizocilpine attenuated withdrawal signs. It indicated that NMDA receptors played an important role in both opiate physical and psychological dependence.