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

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.

To examine possible exercise-induced changes in dopamine signaling, male and female Lewis rats were split into exercise and sedentary groups at 8 wk of age. Exercise rats were run on a treadmill at 10 m·min, 5 d·wk, for 6 wk, whereas sedentary rats remained in their home cage. Rats were killed after the 6 wk of treatment, and their brains were used for in vitro autoradiography using [H]SCH 23,390, [H]Spiperone, and [H]WIN55,428 ligands to quantify dopamine type 1-like receptor (D1R)-like, dopamine type 2-like receptor (D2R)-like, and dopamine transporter binding, respectively.

Exercised rats had 18% and 21% lower D1R-like binding levels compared to sedentary rats within the olfactory tubercle and nucleus accumbens shell, respectively. In addition, male and female exercise rats showed greater D2R-like binding levels within the dorsomedial caudate putamen (30%), ventrolateral caudate putamen (24%), and ventromedial caudate putamen (27%), as well as the olfactory tubercle (19%). Greater D2R-like binding in the nucleus accumbens core (24%) and shell (25%) of exercised rats compared with sedentary rats approached significance. No effects were found for dopamine transporter binding.

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.