Exercise to reduce the escalation of cocaine self-administration in adolescent and adult rats

Abstract

Rationale Concurrent access to an exercise wheel decreases cocaine self-administration under short access (5 h/day for 5 days) conditions and suppresses cocaine-primed reinstatement in adult rats. Objective The effect of exercise (wheel running) on the escalation of cocaine intake during long access (LgA, 6 h/day for 26 days) conditions was evaluated. Methods Adolescent and adult female rats acquired wheel running, and behavior was allowed to stabilize for 3 days. They were then implanted with an iv catheter and allowed to self-administer cocaine (0.4 mg/kg, iv) during 6-h daily sessions for 16 days with concurrent access to either an unlocked or a locked running wheel. Subsequently, for ten additional sessions, wheel access conditions during cocaine self-administration sessions were reversed (i.e., locked wheels became unlocked and vice versa). Results In the adolescents, concurrent access to the unlocked exercise wheel decreased responding for cocaine and attenuated escalation of cocaine intake irrespective of whether the locked or unlocked condition came first. However, cocaine intake increased when the wheel was subsequently locked for the adolescents that had initial access to an unlocked wheel. Concurrent wheel access either before or after the locked wheel access did not reduce cocaine intake in adults. Conclusions Wheel running reduced cocaine intake during LgA conditions in adolescent but not adult rats, and concurrent access to the running wheel was necessary. These results suggest that exercise prevents cocaine seeking and that this effect is more pronounced in adolescents than adults.

Does physical activity protect against drug abuse vulnerability?

“…However, when access to a running wheel is implemented either before or after daily operant conditioning sessions, a decrease in intravenous self-administration also is obtained across different various drugs, including cocaine (Smith et al, 2008b;, methamphetamine (Engelmann et al, 2013;Miller et al, 2012), heroin (Smith and Pitts, 2012) and morphine (Hosseini et al, 2009). Physical activity also decreases the escalation of self-administration (Engelmann et al, 2013;Zlebnik et al, 2012) and reinstatement (Lynch et al, 2010;Sanchez et al, 2013;Thanos et al, 2013;Zlebnik et al, 2010). Especially relevant to human tobacco cessation treatments, physical activity also decreases reinstatement of nicotine seeking following a period of extinction .…”

“…In both rats and mice, the most common method for promoting physical activity is to provide access to a running wheel, although a treadmill or swimming regimen also have been used. The beneficial effect of physical activity is most notable when access to a running wheel occurs during the self-administration session (Cosgrove et al, 2002;Kanarek et al, 1995;Zlebnik et al, 2012). However, when access to a running wheel is implemented either before or after daily operant conditioning sessions, a decrease in intravenous self-administration also is obtained across different various drugs, including cocaine (Smith et al, 2008b;, methamphetamine (Engelmann et al, 2013;Miller et al, 2012), heroin (Smith and Pitts, 2012) and morphine (Hosseini et al, 2009).…”

Effects of combined exercise and progesterone treatments on cocaine seeking in male and female rats

“…Animals were housed and tested in custom-built, octagonally-shaped operant conditioning chambers enclosed in wooden sound-attenuating boxes equipped with ventilation fans as previously described (Zlebnik et al 2010, Zlebnik et al 2012). During cocaine self-administration sessions, responding on the active/drug-paired lever activated the syringe pump (PHM-100, MedAssociates Inc.) to deliver cocaine infusions through a swivel-tether (375/22PS, Instech, Plymouth Meeting, PA, USA, C313CS-MN, PlasticsOne, Roanoke, VA, USA) infusion system that was attached to an infusion harness (CIH95AB, Instech) worn by the rat.…”

“…One to three days after achieving wheel-running behavior, rats were implanted with an indwelling catheter in the right jugular vein following previously published methods (Carroll and Boe 1982, Zlebnik et al 2010, Zlebnik et al 2012). Following the surgical procedure, doors to the wheels remained closed, and each rat was fitted with an infusion harness and tether that remained in place throughout the remainder of the study.…”

“…Controlled laboratory studies in humans demonstrated that moderate-intensity aerobic exercise decreased cravings for alcohol (Ussher et al 2004), cigarettes (Daniel et al 2004), and cannabis (Buchowski et al 2011), while brief episodes of isometric (Ussher et al 2006, Ussher et al 2009) and aerobic (Ussher et al 2001, Daniel et al 2004, Williams et al 2011) exercise also alleviated symptoms of tobacco withdrawal. Studies with animals have also revealed promising treatment effects of exercise on drug-motivated behaviors (Smith and Pitts 2011, Kanarek et al 1995, Miller et al 2011, Cosgrove et al 2002, McMillan et al 1995, Ehringer et al 2009, Smith et al 2011, Zlebnik et al 2012). Reinstatement of cocaine seeking precipitated by exposure to cocaine (Zlebnik et al 2010, Smith et al 2012) or cocaine-paired cues (Lynch et al 2010, Smith et al 2012) was attenuated in exercising rats compared to sedentary rats, and exercise over a withdrawal period also decreased subsequent cocaine seeking (Lynch et al 2010).…”