title: Morphine-Induced Analgesic Tolerance Effect on Gene Expression of the NMDA Receptor Subunit 1 in Rat Striatum and Prefrontal Cortex.
abstract: BACKGROUND
  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).
  
  
  CONCLUSIONS
  Therefore, changes in the NR1 gene expression in rat striatum and PFC have a region-specific association with morphine-induced analgesic tolerance.
authors: Department of Biological Science and Biotechnology, Faculty of Science, University of Kurdistan, Sanandaj, Iran.
authors: Shamseddin
authors: S
authors: Ahmadi
authors: Department of Biological Science and Biotechnology, Faculty of Science, University of Kurdistan, Sanandaj, Iran.
authors: Fatemeh
authors: F
authors: Rafieenia
authors: Department of Biological Science and Biotechnology, Faculty of Science, University of Kurdistan, Sanandaj, Iran.
authors: Jalal
authors: J
authors: Rostamzadeh
keywords: Corpus striatum; Gene expression; Morphine; Prefrontal cortex