Although exercise has been known to regulate brain plasticity, its impact on psychostimulant reward and the associated mesolimbic @entity935 system remained scarcely explored. A psychostimulant, @entity21435 ( @entity14842 ), 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 @entity14842 in male C57BL/6J @entity19 . @entity14842 -induced conditioned place preference (CPP) was used as a behavioral paradigm to indicate the reward efficacy of @entity14842 . We observed that sedentary control @entity19 all demonstrated reliable @entity14842 -induced CPP with our conditioning protocol. Interestingly, pre-exposure to a treadmill exercise decreased the later @entity14842 -induced CPP in a running period-dependent manner. Specifically, @entity19 undergoing a 12-week treadmill running exercise did not exhibit any approaching bias toward the @entity14842 -associated compartment in this CPP paradigm. Twelve weeks of treadmill running did not alter peripheral metabolism of @entity14842 30min following single intraperitoneal injection of @entity14842 (3mg/kg). We further used microdialysis technique to study the underlying mechanisms for the impaired @entity14842 reward produced by the12-week exercise pre-exposure. We found that acute @entity14842 -stimulated @entity935 release in nucleus accumbens was abolished in the exercised @entity19 , whereas an obvious elevation of accumbal @entity935 release was observed in sedentary control @entity19 . Finally, the 12-week exercise program did not alter the protein levels of primary @entity935 receptors, vesicular or membrane transporters in this area. We conclude that the long-term, compulsive exercise is effective in curbing the reward efficacy of @entity14842 possibly via its direct effect on reversing the @entity14842 -stimulated @entity935 release in nucleus accumbens.

Long-term compulsive exercise reduces the rewarding efficacy of XXXX .

@entity935 :: ('MESH:D004298', 'Chemical') :: ['dopamine'] @entity14842 :: ('MESH:D018817', 'Chemical') :: ['MDMA'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity21435 :: ('CHEBI:1391', 'Chemical') :: ['3,4-methylenedioxymethamphetamine']
@entity21435 :: (CHEBI:1391,Chemical) :: ['3,4-methylenedioxymethamphetamine']
