Alterations in the Expression of Calcium Channels and Neurotrophic Factors in the Cerebellum Are Linked to the Induction of Morphine Dependence and Withdrawal

Abstract

Background: Recent studies have shown that the cerebellum directly interacts with the ventral tegmental area, a critical component of the reward system. Objectives: This study aimed to explore potential changes in the expression of neurotrophic factors and various types of voltage-gated calcium channels in the cerebellum following morphine dependence and withdrawal. Methods: This study involved three groups of male Wistar rats. For ten consecutive days, the second and third groups were administered morphine (10 mg/kg), while the first group received saline (1 mL/kg). Analgesic responses were assessed using a hotplate test on days 1 and 10 of the repeated injections and after a 30-day withdrawal period. Rats were sacrificed on day 10 of the injections or on day 30 of withdrawal, and their cerebella were dissected for analysis. Gene expression was analyzed using the real-time PCR method. Results: The study found that morphine analgesia decreased during the 10 days of repeated injections but partially recovered after a 30-day withdrawal period. Morphine dependence led to a decrease in the expression of Cav1.1, which increased after withdrawal. The expression of Cav1.2 in the cerebellum consistently rose after both morphine dependence and withdrawal. There were no significant changes in the expression of Cav2.2 due to morphine dependence or withdrawal. An increase in the expression of Cav3.1 was observed following morphine dependence, which decreased after withdrawal. There were significant reductions in the mRNA levels of neurotrophic factors (BDNF, GDNF, and NGF) and their receptors (TrkB, GFRA1, and NGFR) following morphine dependence. However, the expression of almost all neurotrophic factors increased after morphine withdrawal. Conclusions: The findings suggest that changes in neurotrophic factors, their receptors, and specific types of voltage-gated calcium channels in the cerebellum play roles in the processes of morphine dependency and withdrawal.