Low-dose pretreatment with clorgyline decreases the levels of 3-methoxy-4-hydroxyphenylglycol in the striatum and nucleus accumbens and attenuates methamphetamine-induced conditioned place preference in rats.

The effect of treating rats with clorgyline, an irreversible monoamine oxidase-A (MAO-A) inhibitor, on methamphetamine (METH)-induced conditioned place preference (CPP) was investigated. Administering rats with METH (1.0 mg/kg i.p.) every other day during two conditioning sessions (i.e., saline/METH conditioning with no clorgyline pretreatment) induced a significant CPP compared with saline/saline conditioning. Pretreatment of the rats with clorgyline at a dose of 0.1 mg/kg (i.p.), but not 1.0 or 10 mg/kg, attenuated the METH-induced CPP. Neurochemical analysis using high-performance liquid chromatography revealed that the tissue levels of monoamines and their metabolites were not significantly affected by treatment with 0.1 mg/kg clorgyline except for the levels of 3-methoxy4-hydroxyphenylglycol (MHPG) in the striatum and nucleus accumbens (NAc). Clorgyline at doses of 1.0 or 10 mg/kg significantly affected the tissue levels of 3,4-dihydroxyphenylacetic acid, norepinephrine (NE), MHPG, and serotonin in the cerebral cortex and those of all monoamines and metabolites examined in the striatum and NAc. A significant decrease in the MHPG/NE ratio in the striatum and NAc was apparent in the rats pretreated with 0.1 mg/kg clorgyline. Overall, the present study demonstrated that low-dose clorgyline attenuated METH-induced CPP in rats.