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

Department of Psychology, Davidson College, Davidson, NC 28035, USA.
Drug and alcohol dependence (Impact Factor: 3.28). 08/2011; 121(1-2):54-61. DOI: 10.1016/j.drugalcdep.2011.08.006
Source: PubMed

ABSTRACT 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.
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.
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.

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    • "Prior work has demonstrated a reduction in extinction for females with access to W (Zlebnik et al. 2010) and for both males and females with chronic access to W in the home cage (Smith et al. 2012). Although Smith et al. (2012) showed that W decreased extinction responding in both male and female, their results indicated a stronger effect in females than males with a suppression of responding for a greater period of time (i.e., over more days). Together, the results of the present experiment and those of previous studies demonstrate greater cocaine-motivated responding and greater treatment effects of W in female than in male rats. "
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    ABSTRACT: Individually, both treatment with progesterone and concurrent access to an exercise wheel reduce cocaine self-administration under long-access conditions and suppress cocaine-primed reinstatement in female rats. In the present study, wheel running and progesterone (alone and combined) were assessed for their effects on reinstatement of cocaine-seeking primed by yohimbine, cocaine, and cocaine-paired cues. Male and female rats were implanted with an intravenous catheter and allowed to self-administer cocaine (0.4 mg/kg/inf, iv) during 6-h sessions for 10 days. Subsequently, the groups of male and female rats were each divided into two groups that were given concurrent access to either a locked or unlocked running wheel under extinction conditions for 14 days. Next, all four groups were tested in a within-subjects design for reinstatement of cocaine-seeking precipitated by separate administration of cocaine-paired stimuli, yohimbine, or cocaine or the combination of yohimbine + cocaine-paired stimuli or cocaine + cocaine-paired stimuli. These priming conditions were tested in the presence of concurrent wheel access (W), pretreatment with progesterone (P), or both (W + P). In agreement with previous results, females responded more for cocaine than males during maintenance. Additionally, concurrent wheel running attenuated extinction responses and cocaine-primed reinstatement in females but not in males. Across all priming conditions, W + P reduced reinstatement compared to control conditions, and for cocaine-primed reinstatement in male rats, the combined W + P treatment was more effective than W or P alone. Under certain conditions, combined behavioral (exercise) and pharmacological (progesterone) interventions were more successful at reducing cocaine-seeking behavior than either intervention alone.
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    • "Controlled laboratory studies in humans demonstrated that exercise decreased cravings for alcohol [1], cigarettes [2], and cannabis [3] and alleviated symptoms of tobacco withdrawal [2,4–7]. Further, rodent models of the human drug abuse process have shown that exercise in the form of voluntary wheel running delayed acquisition of cocaine self-administration [8], prevented the escalation of cocaine intake [9] [10], and attenuated reinstatement of cocaine-seeking behavior (relapse) [11] [12] [13]. Long-term daily wheel running also prevented behavioral sensitization to cocaine [14] [15] and decreased motivation to lever-press for cocaine [16] and heroin [17] under a progressive ratio schedule. "
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    ABSTRACT: Emerging evidence from human and animal studies suggests that exercise is a highly effective treatment for drug addiction. However, most work has been done in behavioral models, and the effects of exercise on the neurobiological substrates of addiction have not been identified. Specifically, it is unknown whether prior exercise exposure alters neuronal activation of brain reward circuitry in response to drugs of abuse. To investigate this hypothesis, rats were given 21 days of daily access to voluntary wheel running in a locked or unlocked running wheel. Subsequently, they were challenged with a saline or cocaine (15mg/kg, ip) injection and sacrificed for c-Fos immunohistochemistry. The c-Fos transcription factor is a measure of cellular activity and was used to quantify cocaine-induced activation of reward-processing areas of the brain: nucleus accumbens (NAc), caudate putamen (CPu), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). The mean fold change in cocaine-induced c-Fos cell counts relative to saline-induced c-Fos cell counts was significantly higher in exercising compared to control rats in the NAc core, dorsomedial and dorsolateral CPu, the prelimbic area, and the OFC, indicating differential cocaine-specific cellular activation of brain reward circuitry between exercising and control animals. These results suggest neurobiological mechanisms by which voluntary wheel running attenuates cocaine-motivated behaviors and provide support for exercise as a novel treatment for drug addiction.
    Behavioural brain research 12/2013; 261. DOI:10.1016/j.bbr.2013.12.012 · 3.39 Impact Factor
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    • "Others have suggested that increasing the occurrence of alternative behavior may be an effective approach to the initiation and maintenance of recovery (Bickel and Kelley, 1997; Schuster, 1986). Indeed, a recent report shows that providing access to a running wheel (which presumably functioned as alternative reinforcement) can reduce reinstatement of cocaine responding in rats (Smith et al., 2012). "
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    Behavioural processes 12/2012; 94. DOI:10.1016/j.beproc.2012.12.004 · 1.46 Impact Factor

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