Short- and long-term administration of buprenorphine improved gene expression of P2X4 and GABAA receptors in the hippocampus of methamphetamine rats

Abstract

P2X4 receptors modulate synaptic transmission and communication among neurons in the CNS. An increased level of neuronal P2X4 is associated with altered memory in the hippocampal region. Additionally, some evidence suggests that P2X receptors downregulate the GABAA receptors. In the microglia of drug users, methamphetamine (METH) modifies the expression of certain genes. Therefore, the alterations of P2X4 and GABAA gene expression on memory following treatment with/without buprenorphine (BUP) in METH rats were evaluated. Seventy-seven rats were allocated into eleven groups at random (n = 7). Control, METH (10 mg/kg), BUP (6 and 10 mg/kg) for 5 days, BUP (6 and 10 mg/kg) for 14 days, METH (10 mg/kg) + BUP (6 and 10 mg/kg) for 5 days, METH + BUP (6 and 10 mg/kg) for 14 days and withdrawal group. They received their treatments intraperitoneally. After memory assessment, the animals were decapitated, and the gene expression of P2X4 and GABAA receptors in the hippocampus was assayed using RT-PCR. The memory and P2X4 and GABAA receptor gene expression in METH rats were reduced compared to the control group. The administration of all the different BUP doses increased gene expression in (BUP 6 or 10 mg/kg. 5 days and BUP.10 mg/kg.14 days) + METH groups compared to METH rats. These results demonstrated that METH toxicity severely decreased the level of P2X4 gene expression. Meanwhile, treatment of BUP led to increasing levels of the mentioned gene. Therefore, the potential role of P2X4 and GABAA receptor genes in modulating METH addiction is addressed.

Keywords

• Buprenorphine
• P2X4 receptor
• γ-Amino-butyric acid A
• Hippocampus
• Methamphetamine