Access to a running wheel decreases cocaine-primed and cue-induced reinstatement in male and female rats

Abstract

Background Relapse to drug use after a period of abstinence is a persistent problem in the treatment of cocaine dependence. Physical activity decreases cocaine self-administration in laboratory animals and is associated with a positive prognosis in human substance-abusing populations. The purpose of this study was to examine the effects of long-term access to a running wheel on drug-primed and cue-induced reinstatement of cocaine-seeking behavior in male and female rats. Methods Long-Evans rats were obtained at weaning and assigned to sedentary (no wheel) and exercising (access to wheel) groups for the duration of the study. After 6 weeks, rats were implanted with intravenous catheters and trained to self-administer cocaine for 14 days. After training, saline was substituted for cocaine and responding was allowed to extinguish, after which cocaine-primed reinstatement was examined in both groups. Following this test, cocaine self-administration was re-established in both groups for a 5-day period. Next, a second period of abstinence occurred in which both cocaine and the cocaine-associated cues were withheld. After 5 days of abstinence, cue-induced reinstatement was examined in both groups. Results Sedentary and exercising rats exhibited similar levels of cocaine self-administration, but exercising rats responded less than sedentary rats during extinction. In tests of cocaine-primed and cue-induced reinstatement, exercising rats responded less than sedentary rats, and this effect was apparent in both males and females. Conclusions These data indicate that long-term access to a running wheel decreases drug-primed and cue-induced reinstatement, and that physical activity may be effective at preventing relapse in substance-abusing populations.

Exercise decreases speedball self-administration

“…No differences between sedentary and exercising rats were observed in the initial training sessions on the FR1 schedule of reinforcement, which is consistent with previous studies from our laboratory when rats were trained to lever press prior to surgery (e.g., Smith et al 2008; 2011; 2012). For both exercising and sedentary rats, breakpoints increased linearly as a function of dose when cocaine was tested alone.…”

Exercise as a Potential Treatment for Drug Abuse: Evidence from Preclinical Studies

“…Similarly, Lynch et al (2010) reported that access to a running wheel in the home cage during a 14-day period of forced abstinence was sufficient to reduce both subsequent extinction and cue-induced reinstatement responding in male rats, suggesting that the effects of running last beyond a particular bout of exercise. Consistent with both studies, Smith et al (2011a) reported that long-term access to a running wheel in the home cage (6 weeks before initial drug exposure plus an additional 3 weeks after initial drug exposure) was sufficient to reduce extinction responding, cocaine-primed reinstatement, and cue-induced reinstatement in both male and female rats. Although females tended to exhibit higher levels of responding than males, exercise was an effective intervention in both sexes.…”

“…This effect has been demonstrated in multiple studies employing a variety of experimental parameters (Iversen, 1993; Belke, 1997, 2000; Belke and Dunbar, 2001), and is supported by the observation that laboratory rats, the most common species examined in these studies, will spontaneously run upward of 10 km per day without external inducement (Smith et al, 2011a,b). Exercise also serves as positive reinforcer in humans under some conditions, and like laboratory animals, clinical populations will perform an operant response to engage in aerobic activity (Schebendach et al, 2007).…”

“…In the only study that reported sex differences, concurrent access to a running wheel decreased cocaine self-administration in both males and females, but this effect was only significant in females (Cosgrove et al, 2002). Two other studies reported no sex differences in the effects of exercise on measures of escalation, binge responding, extinction responding, drug-primed reinstatement, and cue-induced reinstatement (Smith et al, 2011a,b). Gonadal hormones are known to influence both drug self-administration (Roberts et al, 1989; Feltenstein and See, 2007; Larson and Carroll, 2007; Mello et al, 2011) and wheel running (Hertrampf et al, 2006; Hydock et al, 2007), but it is not known whether gonadal hormones influence the effects of exercise on drug self-administration.…”

“…The acquisition of regular patterns of drug intake after initial drug exposure can be modeled in the laboratory by exposing an animal to non-contingent drug infusions and then permitting the animal to self-administer that drug in free-operant test sessions. Most studies using exercise as an experimental manipulation failed to report differences in the rate of acquisition between sedentary and exercising animals (Smith et al, 2008, 2011a,b; Zlebnik et al, 2010); however, those studies used protocols designed to maximize the rate of acquisition and minimize any differences between groups (e.g., use of a high training dose, prior lever-press training with food reinforcement, baiting the response lever). Only one study used the rate of acquisition as its primary dependent measure, and that study reported significant differences between sedentary and exercising subjects.…”