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چکیده
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Introduction: Chronic morphine treatment causes tolerance and dependence to the drug. Accumulating evidence suggests an essential role for neurotrophic factor signaling in neuronal adaptations after chronic drug administration. The aim of this study was to examine changes in the gene expression of different neurotrophic factors, including brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and nerve growth factor (NGF) in the striatum and cerebellar cortex after induction of morphine tolerance in rats. Method: We used 16 male Wistar rats in this study. A rat model of morphine tolerance was established after repeated injections of morphine 10 mg/kg (s.c.) twice per day for 10 consecutive days. A control group received saline (1 ml/kg) instead of morphine. On day 10, morphine-induced analgesic tolerance was assessed using a hotplate test of analgesia. Then, each rat was sacrificed, the whole brain was removed, and the striatum and cerebellar cortex were dissected in both groups on day 10 of the schedule. A real-time PCR was used for gene expression assessment. The hotplate data was analyzed with a mixed two-way ANOVA. The real time-PCR data was converted to 2-ΔΔCT value, and then, an independent t-test was used for pairwise comparisons. Statistically significant level was set at P<0.05. Result: Induction of morphine tolerance after 10 days repeated injections of morphine was confirmed with the results of a hotplate test of analgesia compared with the control group (P<0.001). The results of the RT-PCR indicated significant decreases in gene expression of BDNF, GDNF, and NGF in the cerebellar cortex compared with control group (P<0.001). The results also indicated no significant differences in expression of BDNF, GDNF, and NGF in the striatum compared with the saline-treated control group. Conclusion: It can be concluded that repeated morphine treatment affects expression of neurotrophic factors in the cerebellar cortex, but not in the striatum. We propose that changes in neurotrophic factors may have a site-specific involvement in morphine tolerance.
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