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Involvement of sigma 1 receptors in methamphetamine-induced behavioral sensitization in rats.

MS-377 is a novel selective sigma(1) ligand, currently being developed for the treatment of schizophrenia. In the present study, we examined the effects of MS-377 on behavioral sensitization induced by subchronic treatment with methamphetamine. MS-377 was administered at doses of 1.875-15 mg/kg (p.o.), to rats, and methamphetamine was administered at doses of 2 mg/kg (i.p.), 60 min later once daily for 10 days. Repeated administration of methamphetamine caused enhanced stereotypy, and behavioral sensitization was developed. MS-377 did not affect the acute effects of methamphetamine. However, co-administration of MS-377 attenuated the development of methamphetamine-induced behavioral sensitization in a dose-dependent manner. These results suggested that sigma(1) receptors play an important role in the developmental period of behavioral sensitization induced by methamphetamine in rats.