morphine-induced analgesic tolerance effect on gene expression of the nmda receptor subunit 1 in rat striatum and prefrontal cortex

Introduction: morphine is a potent analgesic but its continual use results in analgesic tolerance. mechanisms of this tolerance remain to be clarified. however, changes in the functions of μ-opioid and n-methyl-d-aspartate (nmda) receptors have been proposed in morphine tolerance. we examined changes in gene expression of the nmda receptor subunit 1 (nr1) at mrna levels in rat striatum and prefrontal cortex (pfc) after induction of morphine tolerance.methods: morphine (10 mg/kg, ip) was injected in male wistar rats for 7 consecutive days (intervention group), but control rats received just normal saline (1 ml/kg, ip). we used a hotplate test of analgesia to assess induction of tolerance to analgesic effects of morphine on days 1 and 8 of injections. later, two groups of rats were sacrificed one day after 7 days of injections, their whole brains removed, and the striatum and pfc immediately dissected. then, the nr1 gene expression was examined with a semi-quantitative rt-pcr method.results: the results showed that long-term morphine a administration induces tolerance to analgesic effect of the opioid, as revealed by a significant decrease in morphine-induced analgesia on day 8 compared to day 1 of the injections (p<0.001). the results also showed that the nr1 gene expression at mrna level in rats tolerant to morphine was significantly increased in the striatum (p<0.01) but decreased in the pfc (p<0.001).conclusion: therefore, changes in the nr1 gene expression in rat striatum and pfc have a region-specific association with morphine-induced analgesic tolerance.