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چکیده
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Introduction: Long-term morphine treatment is usually accompanied by morphine tolerance and dependence. Morphine withdrawal causes inability to stop repetitive maladaptive behaviors, which play a major role in the maintenance of and relapse to drug taking. Large-conductance calcium-dependent potassium channels (BK channels) are widely expressed in the central nervous system. Studies have shown that BK channels are responsible for morphine-induced hyperalgesia and anti-nociceptive tolerance. In this study, we aimed to investigate gene expression of different subunits of BK channels, including Kca1, Kcb2, Kcb3, Kcb4 in the striatum after morphine tolerance and withdrawal in rats. Method: Two groups of male Wistar rats received repeated injections of saline (1 ml/kg) or morphine (10 mg/kg) twice daily for 10 days. Induction of morphine tolerance was assessed using a hotplate test of analgesia on day 10. Two other groups of rats after 10 days of the repeated injections of saline or morphine were subjected to 30 days withdrawal. In the rat model of morphine tolerance, each rat was anesthetized on day 10 of the injections, decapitated, and the striatum was dissected on an ice-chilled surface. In the rat model of morphine withdrawal, the striatum was extracted on day 30 after the abstinence. A real-time PCR was used to assess gene expression. A two-way mixed ANOVA was used to analyze the hotplate data. The real time-PCR data was converted to 2-ΔΔCT values, and a paired-group comparison was done with an independent sample t-test. Statistically significant level was set at P<0.05. Results: Real-time PCR results showed that expression of Kca1 in the striatum significantly increased in morphine-tolerant rats (P <0.001), but there were no group differences in expression of Kcb2, Kcb3, Kcb4 in the striatum compared with saline-treated control group. On the other hand, expression of Kca1 in the striatum of morphine-abstinent rats significantly increased compared with the control group (P <0.001). However, expression of Kcb2, Kcb3, Kcb4 significantly decreased compared with the control group (P <0.001). Conclusion: It can be concluded that changes in expression of BK channels in the striatum of rats are involved in morphine tolerance and withdrawal symptoms.
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