Gα protein transduces signals from neurotransmitter receptors and has been implicated in several functions of the central nervous system. In this study, the role of Gα protein in methamphetamine (METH)-induced behavioral sensitization was investigated using neurochemical and behavioral approaches. Repeated treatment with METH (2mg/kg, intraperitoneally) significantly increased behavioral sensitization as well as Gα protein expression and Gα protein activity in the striata of mice, while a single treatment of METH at the same dose did not affect these parameters. Repeated intrastriatal injections of a Gα inhibitor, [D-Trp7,9,10]-substance P, significantly reduced behavioral sensitization and striatal dopamine (DA) level in response to METH, with no effect on striatal tyrosine hydroxylase expression. These results suggest that Gα protein facilitates METH-induced behavioral sensitization by modulating DA release in the mouse striatum.
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