Effect of wheel-running during abstinence on subsequent nicotine-seeking in rats

Abstract

Rationale Exercise appears to be a promising non-pharmacological treatment for nicotine addiction that may be useful for the vulnerable adolescent population. Objectives To determine if wheel running, an animal model of aerobic exercise, during an abstinence period would decrease subsequent nicotine-seeking in rats that had extended access to nicotine self-administration during adolescence. Methods Male adolescent rats (n = 55) were trained to self-administer saline or nicotine infusions (5 or 10 μg/kg) under a fixed ratio 1 schedule with a maximum of 20 infusions/day beginning on postnatal day 30. After 5 days, access was extended to 23-hr/day with unlimited infusions for a total of 10 days. After the last self-administration session, rats were moved to polycarbonate cages for a 10-day abstinence period where they either had access to a locked or unlocked running wheel for 2-hr/day. Nicotine-seeking was examined following the 10th day of abstinence under a within-session extinction/cue-induced reinstatement paradigm. Results Intake was higher at the 10 μg/kg dose as compared to the 5 μg/kg dose; however, intake did not differ within doses prior to wheel assignment. Compared to saline controls, rats that self-administered nicotine at either dose showed a significant increase in drug-seeking during extinction, and consistent with our hypothesis, exercise during abstinence attenuated this effect. Nicotine led to modest, but significant levels of cue-induced reinstatement; however, in this adolescent-onset model, levels were variable and not affected by exercise. Conclusions Exercise may effectively reduce relapse vulnerability for adolescent-onset nicotine addiction.

Chronic wheel running-induced reduction of extinction and reinstatement of methamphetamine seeking in methamphetamine dependent rats is associated with reduced number of periaqueductal gray dopamine neurons

“…The effects of WR were apparent under extinction conditions. This finding is consistent with previous studies in cocaine and nicotine experienced animals, in which WR performed during withdrawal significantly lessened subsequent cocaine and nicotine seeking during extinction (Lynch et al, 2010; Zlebnik et al, 2010; Sanchez et al, 2013). Furthermore, as reported in Lynch et al (2010), our study demonstrates that WR during withdrawal reduces conditioned-cued reinstatement, but significantly extend the findings with methamphetamine, a mechanistically distinct, more potent and toxic stimulant drug of abuse.…”

“…For example, running activity during forced withdrawal reduces cocaine seeking during extinction, and decreases cocaine seeking triggered by drug-cues (Lynch et al, 2010; Thanos et al, 2013) and cocaine itself in cocaine experienced rats (Thanos et al, 2013). However, WR during forced withdrawal reduced nicotine seeking during extinction and did not alter nicotine seeking triggered by drug-cues (Sanchez et al, 2013) in nicotine experienced rats, suggesting that WR’s efficacy may vary by the drug self-administered. The purpose of the present study was to characterize the effects of WR during forced withdrawal on methamphetamine seeking during extinction and methamphetamine seeking triggered by drug-context and drug-cues in methamphetamine dependent rats.…”

Voluntary wheel running reduces voluntary consumption of ethanol in mice: identification of candidate genes through striatal gene expression profiling

“…Wheel running in rodents has been shown to induce a myriad of behavioral responses related to tests of stress, anxiety, and depression (Adlard and Cotman, 2004; Brené et al, 2007; Clark et al, 2015; Dishman et al, 2006; Greenwood et al, 2011, 2013; Hare et al, 2014; Lapmanee et al, 2013; Loughridge et al, 2013; Mika et al, 2015; Sciolino et al, 2015; Sierakowiak et al, 2014). Furthermore, previous studies have demonstrated wheel running was sufficient to reduce voluntary intake of amphetamine (Kanarek et al, 1995), cocaine (Cosgrove et al, 2002; Smith et al, 2011), as well as nicotine-seeking during extinction (Sanchez et al, 2013; Smith and Lynch, 2011). Taken together with the effects of wheel running on ethanol behaviors, observed across multiple species (Darlington et al, 2014; Ehringer et al, 2009; Gallego et al, 2015; Hammer et al, 2010; McMillan et al, 1995; Weinstock, 2010; Werme et al, 2002), these data show clear evidence of hedonic substitution.…”

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 .…”