Long-term compulsive exercise reduces the rewarding efficacy of 3,4-methylenedioxymethamphetamine.
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 30min following single intraperitoneal injection of MDMA (3mg/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.
Chen
Hsiun Ing
HI
Department of Physiology, National Cheng Kung University College of Medicine, Tainan 701, Taiwan, ROC.
Kuo
Yu Min
YM
Liao
Chung-Hsien
CH
Jen
Chauying J
CJ
Huang
A Min
AM
Cherng
Chianfang G
CG
Su
Shu-Wen
SW
Yu
Lung
L
D018759:Adrenergic Uptake Inhibitors / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D009043:Motor Activity / Q000502:physiology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000097:blood / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D012201:Reward
D018759:Adrenergic Uptake Inhibitors; D050483:Dopamine Plasma Membrane Transport Proteins; D026901:Membrane Transport Proteins; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine