ALTERATIONS OF PI3K {PHOSPHATIDYLINOSITOL 3 KINASE (PI3K)} PROTEIN KINASE B /AKT GENE EXPRESSION DURING BUPRENORPHINE MODULATED METHAMPHETAMINE ADDICTION IN RAT

Background and Aim : Methamphetamine (MA) is one of the commonly used illicit drugs and the central nervous system toxicity of MA is well documented. Buprenorphine, a partial mu-opioid receptor agonist, has unique pharmacologic properties and it is used in the treatment of opioid dependence. The PI3K-protein kinase B (Akt) signaling pathway regulates numerous biological processes, including cell survival, proliferation and has been demonstrated to be involved in the neuronal adaptations that underlie drug related behaviors such as reward seeking and excessive drug intake. In this study, we investigated the effect of MA and buprenorphine on the expression levels of the PI3K/ Akt in the lumbar segment of the spinal cord of a male rats. Methods : 49 male Wistar rats were randomly assigned into seven experimental groups (n=7): Control, Saline, Methamphetamine (10 mg/kg, i.p. for 5 days), Buprenorphine (6 and 10 mg/kg, i.p.), Methamphetamine + Buprenorphine (6 and 10 mg/kg for 14 days). Lumbar spinal tissues were assayed for the expression of PI3K /Akt gene using RT- PCR. Results : Results showed that chronic administration of methamphetamine increased the Akt gene expression in comparison to control group (p<0.01). Administration of 6mg/kg of buprenorphine did not change the expression level of Akt. Also, the expression of PI3K /Akt gene was increased after the buprenorphine (10 mg/kg) administration (p<0.01). In other two methamphetamine addicted groups, administration of buprenorphine with two doses (6 and 10 mg/kg) for 14 days decreased the level of AKt gene expression in comparison to methamphetamine or addicted groups (p<0.05). Conclusion : It seems that PI3K/AKt pathway plays a critical role in the development of methamphetamine toxicity. Buprenorphine by reducing the level of PI3K/AKt gene expression in addicted group, may be involved in reducing of proinflammatory cytokines and has neuroprotective effects in treatment of psychostimulant drugs