Guanine nucleotide-binding regulatory proteins (G proteins) play an obligatory role in the transmembrane signaling system and are concerned with the neurochemical basis of several psychiatric disorders. We examined the alteration in the mRNA levels of G protein subclasses (Gil alpha, Gi2 alpha and Go alpha) in behavioral sensitized rats using subchronic treatment with methamphetamine (MAP). Adult male Sprague-Dawley rats received intraperitoneal injections of MAP (4 mg/kg) or saline (control) once daily for 14 days. A remarkable increase in the levels of Gi2 alpha mRNA was observed in both sides of striatum at 48 hours after the last injection of MAP. The changes in the Gi2 alpha mRNA levels were not significant at two weeks after the last injection of MAP. The levels of Go alpha and Gil alpha mRNA were not changed at 48 hours and at two weeks after the last injection of MAP. These results suggest that the changes in the Gi2 mRNA level might be responsible for the reinforcement of the generation of stereotyped abnormal behavior by repeated administration of MAP rather than the persistence of the reverse tolerance phenomenon.