TY - JOUR
T1 - Long-term compulsive exercise reduces the rewarding efficacy of 3,4-methylenedioxymethamphetamine
AU - Chen, Hsiun Ing
AU - Kuo, Yu Min
AU - Liao, Chung Hsien
AU - Jen, Chauying J.
AU - Huang, A. Min
AU - Cherng, Chianfang G.
AU - Su, Shu Wen
AU - Yu, Lung
N1 - Funding Information:
We thank Dr. J.I. Chuang for her constructive criticisms on the manuscript, and Ms. H.-W. Chen and L.-C. Wu for their technical assistance. This study was supported by National Science Council in Taiwan (Grants no. NSC92-2321-B-006-001, NSC93-2321-B-006-005, NSC92-2321-B-006-004, and NSC93-2321-B-006-008).
PY - 2008/2/11
Y1 - 2008/2/11
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbr.2007.09.014
DO - 10.1016/j.bbr.2007.09.014
M3 - Article
C2 - 17949827
AN - SCOPUS:36749004289
VL - 187
SP - 185
EP - 189
JO - Behavioural Brain Research
JF - Behavioural Brain Research
SN - 0166-4328
IS - 1
ER -