Exercise Reduces Dopamine D1R and Increases D2R in Rats: Implications for Addiction

Introduction Exercise has been shown to be effective for preventing and treating substance abuse in both clinical and preclinical studies. Less is known, however, regarding the underlying neurobiological mechanisms driving these changes in drug-seeking behavior. One possibility is that exercise may alter the mesolimbic dopamine pathway in such a way that makes drugs of abuse less salient and/or rewarding. Methods To examine possible exercise-induced changes in dopamine signaling, male and female Lewis rats were split into exercise and sedentary groups at 8 weeks of age. Exercise rats were run on a treadmill at 10m/min, five days per week, for six weeks, while sedentary rats remained in their home cage. Rats were euthanized following the 6 weeks of treatment, and their brains were used for in vitro autoradiography using [3H]SCH 23,390, [3H]Spiperone, and [3H]WIN55,428 ligands to quantify D1R-like, D2R-like, and dopamine transporter (DAT) binding, respectively. Results Exercised rats had 18% and 21% lower D1R-like binding levels compared to sedentary rats within the olfactory tubercle (OT) and nucleus accumbens shell (AcbS), respectively. In addition, male and female exercise rats showed greater D2R-like binding levels within the dorsomedial (DM CPu; 30%), ventrolateral (VL CPu; 24%), and ventromedial (VM CPu; 27%) caudate putamen, as well as the OT (19%). Greater D2R-like binding in the nucleus accumbens core (AcbC; 24%) and shell (AcbS; 25%) of exercised rats compared to sedentary rats approached significance. No effects were found for DAT binding. Conclusions These findings support the hypothesis that aerobic exercise results in changes in the mesolimbic pathway that could mediate exercise-induced attenuation of drug-seeking behavior. Correspondence should be addressed to: Panayotis K. Thanos, Address: 1021 Main Street, Buffalo, NY 14203-1016, Email: pthanos@ria.buffalo.edu This research was funded by the NY Research Foundation (RIAQ094O). The authors report no conflicts of interest. The results of the present study do not constitute endorsement by ACSM. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for Publication: 23 May 2018 © 2018 American College of Sports Medicine

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