Inhibition of methamphetamine-induced hyperlocomotion in mice by clorgyline, a monoamine oxidase-a inhibitor, through alteration of the 5-hydroxytriptamine turnover in the striatum.

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.