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

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Abstract

Rationale and objective

Whether 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 methods

Since 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.

Results

Fourteen 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.

Conclusions

We 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.

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Acknowledgments

This research is supported by ROC National Science Council grants 952413H006003MY2 and 952320B006042 to L.Y.

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Correspondence to Lung Yu.

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Ho, MC., Cherng, C.G., Tsai, YP.N. et al. Chronic treatment with monoamine oxidase-B inhibitors decreases cocaine reward in mice. Psychopharmacology 205, 141–149 (2009). https://doi.org/10.1007/s00213-009-1524-5

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  • DOI: https://doi.org/10.1007/s00213-009-1524-5

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