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.&nbsp;Mechanisms of this tolerance remain to be clarified. However, changes in the functions of&nbsp;&mu;-opioid and N-Methyl-D-aspartate (NMDA) receptors have been proposed in morphine&nbsp;tolerance. We examined changes in gene expression of the NMDA receptor subunit 1 (NR1) at&nbsp;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&nbsp;(intervention group), but control rats received just normal saline (1 mL/kg, IP). We used a&nbsp;hotplate test of analgesia to assess induction of tolerance to analgesic effects of morphine on days&nbsp;1 and 8 of injections. Later, two groups of rats were sacrificed one day after 7 days of injections,&nbsp;their whole brains removed, and the striatum and PFC immediately dissected. Then, the NR1&nbsp;gene expression was examined with a semi-quantitative RT-PCR method. Results: The results showed that long-term morphine a administration induces tolerance to&nbsp;analgesic effect of the opioid, as revealed by a significant decrease in morphine-induced analgesia&nbsp;on day 8 compared to day 1 of the injections (P<0.001). The results also showed that the NR1&nbsp;gene expression at mRNA level in rats tolerant to morphine was significantly increased in the&nbsp;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&nbsp;region-specific association with morphine-induced analgesic tolerance.