Introduction: A growing body of evidence shows that voltage-gated calcium channels are implicated in actions of morphine on neurons, but their involvement in opioid withdrawal have remained uncertain. Different brain regions including the striatum and cerebellum are affected by morphine. The aim of this study was to examine and compare possible changes in the gene expression of different voltage-gated calcium channels, including Cav1.1, Cav1.2, Cav2.2, and Cav3.1 in the striatum and cerebellar cortex after morphine withdrawal in rats. Method: Sixteen male Wistar rats were randomly assigned into two experimental groups. Rats in two experimental groups received repeated injections of either saline (1 ml/kg) or morphine (10 mg/kg) for ten consecutive days twice daily with eight-hour intervals at 8:30 and 16:30. Induction of dependence to the repeated injections of morphine was assessed with naloxone-precipitated withdrawal test on day 10. Then, rats were subjected to 30 days withdrawal period. On day 30 of the withdrawal, each rat was sacrificed, the whole brain was removed, and the striatum and cerebellar cortex were dissected on an ice-chilled surface. The gene expression was examined using a quantitative RT-PCR method. The data was analyzed using an independent sample t-test. P<0.05 was set as a statistically significant level. Result: The results of the RT-PCR indicated significant increases in expression of Cav1.1 and Cav1.2 (P<0.001), but a significant decrease in mRNA level of Cav3.1 (P<0.001) in the cerebellar cortex in morphine-abstinent rats compared with the saline-treated control group. No group difference was detected for expression of Cav2.2 between the experimental groups. The results also indicated significant decrease in Cav1.1, Cav2.2, and Cav3.1 mRNA level (P<0.001) in morphine-abstinent rats compared to the saline control group. There was no group difference in expression of Cav1.2 in the striatum between experimental groups. Conclusion: It can be concluded that morphine withdrawal affects the expression of voltage-gated calcium channels in the cerebral cortex and striatum. However, gene differences were region specific in the cerebellum and striatum. We suggest that calcium channels in the cerebellum and striatum have important roles in morphine withdrawal signs and relapse, which need to be more investigated.
