Chronic treatment with monoamine oxidase-B inhibitors decreases cocaine reward in mice.

RATIONALE AND

objectiveWhether monoamine oxidase inhibitors (MAOIs) can be used to suppress the reinforcing effect of cocaine remains unknown. This study was undertaken to examine effects of a long-term dosing regimen with selective MAOIs on cocaine and food reward. MATERIALS AND

methodsSince single dose of clorgyline (2 mg/kg), deprenyl (1 mg/kg), and pargyline (10 mg/kg) did not acutely affect mouse locomotor activity, these doses were chosen to treat the male C57BL/6j mice on a daily basis.

resultsFourteen consecutive days of pretreatments with clorgyline, deprenyl, or pargyline (one injection per day) did not affect natural reward-supported operant behavior, since acquisition of the lever pressing responses for food pellets under an FR-1 protocol did not differ among these drug- and saline-treated mice. Likewise, 24 consecutive days of pretreatments with clorgyline did not alter acquisition of the cocaine (0.3 mg/kg per infusion)-supported operant responses under an FR-1 protocol. In contrast, 24 days of pretreatments with deprenyl and pargyline abolished the cocaine-supported operant responses under a similar protocol. Twenty-four days of clorgyline treatment enhanced serotonin contents in striatum, nucleus accumbens, and frontal cortex. Frontal cortical 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacidic acid concentrations were decreased following 24 days of pretreatments with deprenyl and pargyline. These changes were not evident in mice pretreated with clorgyline.

conclusionsWe suggest that long-term treatments with MAO-B inhibitors may decrease cocaine-supported operant responses in cocaine-naïve mice by selectively decreasing frontal cortical metabolism of dopamine and serotonin.