The psychomotor stimulant methamphetamine (METH) has been shown to cause specific behaviors such as hyperlocomotion in rodents. Pretreatment of repeated s.c. administration of clorgyline (1 mg/kg, once per day for 5 consecutive days), a monoamine oxidase (MAO)-A inhibitor, blocked hyperlocomotion induced by a single i.p. administration of METH (1 mg/kg) in male ICR mice, without any effect on spontaneous locomotion. The blockade was also observed when mice were pretreated with a single administration of clorgyline (1 mg/kg, s.c.), without potentiating hyperlocomotion and rearing induced by a single challenge of METH at the range of 0.5-2 mg/kg (i.p.). In contrast, single or repeated pretreatment of selegiline (0.3 mg/kg, s.c.), a MAO-B inhibitor, had no effect on METH-induced hyperlocomotion. Clorgyline pretreatment, both single and repeated, altered the effects of single METH challenges on apparent 5-hydroxytryptamine (serotonin) turnover in the region of the striatum and accumbens. These results suggest that clorgyline tends to oppose METH-induced hyperlocomotion through alteration of the serotonergic system in the region of the striatum and accumbens.