Long-term compulsive exercise reduces the rewarding efficacy of 3,4-methylenedioxymethamphetamine

Hsiun Ing Chen, Yu Min Kuo, Chung Hsien Liao, Chauying J. Jen, A. Min Huang, Chianfang G. Cherng, Shu Wen Su, Lung Yu

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Although exercise has been known to regulate brain plasticity, its impact on psychostimulant reward and the associated mesolimbic dopamine system remained scarcely explored. A psychostimulant, 3,4-methylenedioxymethamphetamine (MDMA), is currently a worldwide abused drug of choice. We decided to examine the modulating effects of long-term, compulsive treadmill exercise on the hedonic value of MDMA in male C57BL/6J mice. MDMA-induced conditioned place preference (CPP) was used as a behavioral paradigm to indicate the reward efficacy of MDMA. We observed that sedentary control mice all demonstrated reliable MDMA-induced CPP with our conditioning protocol. Interestingly, pre-exposure to a treadmill exercise decreased the later MDMA-induced CPP in a running period-dependent manner. Specifically, mice undergoing a 12-week treadmill running exercise did not exhibit any approaching bias toward the MDMA-associated compartment in this CPP paradigm. Twelve weeks of treadmill running did not alter peripheral metabolism of MDMA 30 min following single intraperitoneal injection of MDMA (3 mg/kg). We further used microdialysis technique to study the underlying mechanisms for the impaired MDMA reward produced by the12-week exercise pre-exposure. We found that acute MDMA-stimulated dopamine release in nucleus accumbens was abolished in the exercised mice, whereas an obvious elevation of accumbal dopamine release was observed in sedentary control mice. Finally, the 12-week exercise program did not alter the protein levels of primary dopamine receptors, vesicular or membrane transporters in this area. We conclude that the long-term, compulsive exercise is effective in curbing the reward efficacy of MDMA possibly via its direct effect on reversing the MDMA-stimulated dopamine release in nucleus accumbens.

Original languageEnglish
Pages (from-to)185-189
Number of pages5
JournalBehavioural Brain Research
Volume187
Issue number1
DOIs
Publication statusPublished - 2008 Feb 11

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

Fingerprint Dive into the research topics of 'Long-term compulsive exercise reduces the rewarding efficacy of 3,4-methylenedioxymethamphetamine'. Together they form a unique fingerprint.

Cite this