Nociceptive threshold response and alterations of special genes expression during methamphetamine administration and treatment with buprenorphine

Methamphetamine is a nerve stimulant. Buprenorphine has been widely used in the management of various types of pain and reducing addiction side effects. This study aimed to investigate the role of methamphetamine, buprenorphine, or their interaction on analgesic threshold and the expression of protein kinase B (AKT) and glycogen synthase kinase 3 (GSK3b) genes in the lumbar spinal cord of male rats. Materials and Methods: In this experimental study, 56 male Wistar rats (weight 200 ± 50 g) were randomly divided into eight groups: The control group, sham group, methamphetamine group, two buprenorphine groups, two methamphetamines + buprenorphine groups, and deprivation group. The drugs of methamphetamine and buprenorphine were injected intraperitoneal (i.p) for five days. To measure the analgesic threshold, the Tail-Flick test was used. Additionally, the real-time PCR technique was applied to evaluate the expression levels of AKT and GSK3b genes in the lumbar spinal cord of male rats. A one-way ANOVA test was used to analyze the data. Results: Intraperitoneal injection of methamphetamine (10 mg/kg) induced analgesia (P < 0.05) and increased the expression of the gene of AKT (P < 0.05) in the lumbar spinal cord of male rats. In addition, the injection of buprenorphine (6 and 10 mg/kg) potentiated the effect of methamphetamine on analgesia (P < 0.01) and increased the expression of the GSK3b gene (P < 0.05), whereas the higher dose of buprenorphine reduced the impact of methamphetamine on the expression of AKT gene (P < 0.05). Furthermore, the deprivation of methamphetamine, did not alter Tail Flick latency and the expression level of AKT and GSK3b genes. Conclusion: Our results indicated a possible reinforcing role of the buprenorphine on the increasing impact of acute methamphetamine injection on the expression of the GSK3b gene and analgesia.