Short- and long-term administration of buprenorphine improved gene expression of P ₂X ₄ and GABAA receptors in the hippocampus of methamphetamine rats

Abstract

P ₂X ₄ receptors modulate synaptic transmission and communication among neurons in the CNS. An increased level of neuronal P ₂X ₄ is associated with altered memory in the hippocampal region. Additionally, some evidence suggests that P ₂X receptors downregulate the GABA _A receptors. In the microglia of drug users, methamphetamine (METH) modifies the expression of certain genes. Therefore, the alterations of P ₂X ₄ and GABA _A 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 P ₂X ₄ and GABA _A receptors in the hippocampus was assayed using RT-PCR. The memory and P ₂X ₄ and GABA _A 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 P ₂X ₄ gene expression. Meanwhile, treatment of BUP led to increasing levels of the mentioned gene. Therefore, the potential role of P ₂X ₄ and GABA _A receptor genes in modulating METH addiction is addressed.

Abstract

Buprenorphine; P ₂X ₄ receptor; γ-Amino-butyric acid A; Hippocampus; Methamphetamine.