Reciprocal inhibitory effects of intravenous d-methamphetamine self-administration and wheel activity in rats

Abstract

Background Some epidemiological and cessation studies suggest physical exercise attenuates or prevents recreational drug use in humans. Preclinical studies indicate wheel activity reduces cocaine self-administration in rats; this may, however, require the establishment of compulsive wheel activity. Methods Effects of concurrent wheel activity on intravenous d-methamphetamine (METH) self-administration were examined in male Wistar and Sprague Dawley rats with negligible prior wheel experience. Wistar rats self-administered METH (0.05 mg/kg/inf) under a fixed-ratio 1 (FR1) schedule with concurrent access to an activity wheel during sessions 1–14, 8–21 or 15–21. Control rats which did not self-administer METH had access to an activity wheel during sessions 1–14, 8–21 or 15–28. Sprague Dawley rats self-administered METH (0.1 mg/kg/inf) under FR1 for 14 sessions with either concurrent access to a locked or an unlocked activity wheel. Results METH self-administration was lower when the wheel was available concurrently from the start of self-administration training in both strains, even though Sprague Dawley rats self-administered twice as many METH infusions and ran one-sixth as much on the wheel compared to Wistar rats. Wheel access initiated after 7 or 14 days had no effect on METH self-administration in Wistar rats. Wheel activity was significantly reduced in these groups compared with the group with concurrent wheel and METH access for the first 14 sessions. Conclusions These data show METH self-administration is reduced by exercise if initiated from the start of self-administration and that prior METH self-administration experience interferes with the value of exercise as a reinforcer.

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

“…In that study, the relationship between exercise and cocaine self-administration was reciprocal, in that concurrent access to cocaine also decreased wheel running, and this effect was observed in both males and females. Consistent with those findings, Miller et al (2011) reported that concurrent access to a running wheel decreased responding maintained by methamphetamine, provided that the wheel was concurrently available at the outset of self-administration training. Using a slightly different experimental design, Smith et al (2008) reported that aerobic exercise reduced cocaine self-administration even when a running wheel was not concurrently available during the test sessions.…”

“…It is important to note that in studies in which exercise was used as an alternative reinforcer, the decrease in drug self-administration could not be attributed to simply having less time available to self-administer the drug. In all existing studies, test sessions lasted several hours or longer (e.g., Kanarek et al, 1995; Cosgrove et al, 2002; Zlebnik et al, 2010; Miller et al, 2011), and the cumulative amount of time spent on both activities was less than the total duration of the session. Consequently, the ability of exercise to decrease drug self-administration is generally attributed to a decrease in the relative reinforcing strength of the drug when both are concurrently available.…”

Does physical activity protect against drug abuse vulnerability?

“…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). 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).…”

Exercise decreases speedball self-administration

“…Preclinical studies have supported these findings by reporting that exercise, which is typically operationalized as running on a treadmill or in an activity wheel, decreases the self-administration of many drugs of abuse. In laboratory rats, for instance, exercise reliably decreases the positive reinforcing effects of psychomotor stimulants, including cocaine and methamphetamine (Cosgrove et al 2002; Miller et al 2012; Smith and Witte 2012; Smith et al 2008; 2011), and the positive reinforcing effects of opioids, including heroin and morphine (Hosseini et al 2009; Smith and Pitts 2012). Moreover, these effects are typically observed across doses, subject populations, and schedules of reinforcement (for review, see Lynch et al 2013; Smith and Lynch 2012).…”