Methamphetamine induces long-term changes in GABAA receptor α2 subunit and GAD67 expression

The present study investigated whether GABAA receptor α2 subunit and GAD67 are involved in chronic high dose methamphetamine (METH)-induced sensitization and neurotoxicity. The METH sensitization was established in rats by 7-day pump infusion plus daily injection (25 mg/kg/day) and a subsequent 28-day withdrawal period. Behavioral sensitization was assessed by behavioral ratings after challenge with METH (0.5 mg/kg). The neurotoxicity was evaluated by the expression of glial fibrillary acidic protein (GFAP). Western blot assay showed that METH sensitization decreases GABAA α2 subunit and GAD67 protein levels in the nucleus accumbens (NAc) core and shell, and conversely, these proteins were increased in the caudate. An upregulation of GFAP expression was observed in the caudate, but not in the NAc core and shell. These data suggest that inhibition of GABA transmission in the NAc is related to METH behavioral sensitization, whereas activation of GABA transmission in the caudate is associated with METH-induced neurotoxicity.