The effects of resistance exercise on cocaine self-administration, muscle hypertrophy, and BDNF expression in the nucleus accumbens

Abstract

Background Exercise is associated with positive outcomes in drug abusing populations and reduces drug self-administration in laboratory animals. To date, most research has focused on aerobic exercise, and other types of exercise have not been examined. This study examined the effects of resistance exercise (strength training) on cocaine self-administration and BDNF expression, a marker of neuronal activation regulated by aerobic exercise. Methods Female rats were assigned to either exercising or sedentary conditions. Exercising rats climbed a ladder wearing a weighted vest and trained six days/week. Training consisted of a three-set “pyramid” in which the number of repetitions and resistance varied across three sets: eight climbs carrying 70% body weight (BW), six climbs carrying 85% BW, and four climbs carrying 100% BW. Rats were implanted with intravenous catheters and cocaine self-administration was examined. Behavioral economic measures of demand intensity and demand elasticity were derived from the behavioral data. BDNF mRNA expression was measured via qRT-PCR in the nucleus accumbens following behavioral testing. Results Exercising rats self-administered significantly less cocaine than sedentary rats. A behavioral economic analysis revealed that exercise increased demand elasticity for cocaine, reducing consumption at higher unit prices. Exercising rats had lower BDNF expression in the nucleus accumbens core than sedentary rats. Conclusions These data indicate that resistance exercise decreases cocaine self-administration and reduces BDNF expression in the nucleus accumbens after a history of cocaine exposure. Collectively, these findings suggest that strength training reduces the positive reinforcing effects of cocaine and may decrease cocaine use in human populations.

Exercise as a Prevention for Substance Use Disorder: a Review of Sex Differences and Neurobiological Mechanisms

“…Drug use escalation, or a progressive increase in drug intake over time, is believed to mimic excessive/uncontrolled drug use typical of human substance use disorder (33) and can be captured in animals by extending the access to the drug (≥6 hr/day). While most of this work has focused on aerobic exercise via voluntary wheel running or forced treadmill running (e.g., 34–35), recent work has examined effects of resistance exercise using a weighted ladder-climbing procedure (36). …”

“…Effects on chromatin containing the Bdnf gene in particular has been implicated in mediating persistent protection against drug use, particularly in males (67). Both drugs of abuse and exercise modulate Bdnf (68–69), and recent evidence show that resistance exercise affects drug-induced changes in Bdnf expression in female rats (36). …”

Animal models of resistance exercise and their application to neuroscience research

“…Whereas many ladder-climbing procedures use noxious stimuli (e.g., electric shock, food deprivation) to maintain behavior, others have successfully maintained climbing without the repeated use of potentially painful stimuli (Cassilhas et al, 2012a, 2012b, 2013; Nokia et al, 2016; Strickland et al, 2016). For example, our laboratory recently used a modified climbing protocol in which rats were trained to climb a ladder (46 cm long, 90° incline) with a dark chamber at the top and a bright light positioned at the bottom of the ladder to motivate subjects to climb (Strickland et al, 2016).…”

“…For example, our laboratory recently used a modified climbing protocol in which rats were trained to climb a ladder (46 cm long, 90° incline) with a dark chamber at the top and a bright light positioned at the bottom of the ladder to motivate subjects to climb (Strickland et al, 2016). In this study, sessions were conducted 6 days per week with 3 sets performed at increasing loads attached to a weighted harness: 8 climbs at 70% BW, 6 climbs at 85% BW, and 4 climbs at 100% BW.…”

“…These studies have typically supported the human literature and revealed protective effects of aerobic training on measures of drug-seeking and drug-taking behavior (see reviews by Lynch et al, 2013; Smith and Lynch, 2012). Recently, we evaluated the effects of a ladder-climbing procedure (see Section 3.2) on cocaine self-administration in laboratory rats (Strickland et al, 2016). Exercising rats in that study self-administered significantly less cocaine than sedentary subjects receiving equal handling and exposure to the ladder apparatus without resistance climbing.…”