Daily treadmill exercise attenuates cocaine cue-induced reinstatement and cocaine induced locomotor response but increases cocaine-primed reinstatement.

Exercise affects neuroplasticity and neurotransmission including dopamine (DA), which modulates drug-taking behavior. Previous research in rodents has shown that exercise may attenuate the rewarding effects of drugs of abuse. The present study examined the effects of high and low exercise on cocaine responses in male Wistar rats that had been trained to self-administer and were compared to a group of sedentary rats. High exercise rats (HE) ran daily on a treadmill for 2h and low exercise (LE) ran daily for 1h. After 6 weeks of this exercise regimen, rats were tested over 2 days for reinstatement (day 1: cue-induced reinstatement; day 2: cocaine-primed reinstatement). During cue-induced reinstatement, the sedentary rats showed the expected increase in active lever responses when compared to maintenance, whereas these increased responses were inhibited in the exercised rats (HE and LE). During cocaine-primed reinstatement, however, there was a significant increase in active lever presses when compared to maintenance only in the HE group. This data suggests that chronic exercise during abstinence attenuates the cue-induced reinstatement seen in the sedentary rats by 26% (LE) and 21% (HE). In contrast, only the high exercise rats exhibited sensitized cocaine-seeking behavior (active lever presses) following cocaine-primed reinstatement. Finally, while sedentary rats increased locomotor activity during cocaine-primed reinstatement over that seen with cocaine during maintenance, this was not observed in the exercised rats, suggesting that exercise may interfere with the sensitized locomotor response during cocaine reinstatement.