PMID- 17949827 OWN - NLM STAT- MEDLINE DCOM- 20080311 LR - 20220311 IS - 0166-4328 (Print) IS - 0166-4328 (Linking) VI - 187 IP - 1 DP - 2008 Feb 11 TI - Long-term compulsive exercise reduces the rewarding efficacy of 3,4-methylenedioxymethamphetamine. PG - 185-9 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 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. FAU - Chen, Hsiun Ing AU - Chen HI AD - Department of Physiology, National Cheng Kung University College of Medicine, Tainan 701, Taiwan, ROC. FAU - Kuo, Yu Min AU - Kuo YM FAU - Liao, Chung-Hsien AU - Liao CH FAU - Jen, Chauying J AU - Jen CJ FAU - Huang, A Min AU - Huang AM FAU - Cherng, Chianfang G AU - Cherng CG FAU - Su, Shu-Wen AU - Su SW FAU - Yu, Lung AU - Yu L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070916 PL - Netherlands TA - Behav Brain Res JT - Behavioural brain research JID - 8004872 RN - 0 (Adrenergic Uptake Inhibitors) RN - 0 (Dopamine Plasma Membrane Transport Proteins) RN - 0 (Membrane Transport Proteins) RN - 0 (Receptors, Dopamine D1) RN - 0 (Receptors, Dopamine D2) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Adrenergic Uptake Inhibitors/blood/*pharmacology MH - Animals MH - Blotting, Western MH - Conditioning, Operant/drug effects MH - Dopamine/metabolism MH - Dopamine Plasma Membrane Transport Proteins/drug effects/metabolism MH - Male MH - Membrane Transport Proteins/drug effects/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Microdialysis MH - Motor Activity/physiology MH - N-Methyl-3,4-methylenedioxyamphetamine/blood/*pharmacology MH - Nucleus Accumbens/drug effects/metabolism MH - Physical Conditioning, Animal/*physiology MH - Receptors, Dopamine D1/drug effects/metabolism MH - Receptors, Dopamine D2/drug effects/metabolism MH - *Reward EDAT- 2007/10/24 09:00 MHDA- 2008/03/12 09:00 CRDT- 2007/10/24 09:00 PHST- 2007/07/11 00:00 [received] PHST- 2007/08/30 00:00 [revised] PHST- 2007/09/07 00:00 [accepted] PHST- 2007/10/24 09:00 [pubmed] PHST- 2008/03/12 09:00 [medline] PHST- 2007/10/24 09:00 [entrez] AID - S0166-4328(07)00490-1 [pii] AID - 10.1016/j.bbr.2007.09.014 [doi] PST - ppublish SO - Behav Brain Res. 2008 Feb 11;187(1):185-9. doi: 10.1016/j.bbr.2007.09.014. Epub 2007 Sep 16.