Resistance exercise decreases heroin self-administration and alters gene expression in the nucleus accumbens of heroin-exposed rats

Smith, Mark A.; Fronk, Gaylen; Abel, Jean M.; Lacy, Ryan T.; Bills, Sarah E.; Lynch, Wendy J.

doi:10.1007/s00213-018-4840-9

Cited by 24 publications

(26 citation statements)

References 73 publications

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“…6). Neurobiologically, exercise activates the same mesolimbic dopamine pathways as drug abuse (e.g., Di Chiara and Imperato 1988;Park et al 2016) and results in long-term neuroadaptations in this pathway and the prefrontal cortex (Peterson et al 2014a) that may reduce the reinforcing efficacy of drugs of abuse (Smith and Lynch 2012;Zlebnik et al 2014a;Robertson et al 2016;Smith et al 2018). Since wheel access was available both inside and outside the experimental session, it is likely that both behavioral and neurobiological mechanisms played some role in the present study.…”

Section: Discussionmentioning

confidence: 93%

“…Results indicated that exercise reduced spontaneous withdrawal signs (Balter and Dykstra 2012;Miladi-Gorji et al 2012;Mokhtari-Zaer et al 2014;Fadaei et al 2015;Alizadeh et al 2018) and oral morphine consumption (Fadaei et al 2015). Related findings by Smith and colleagues have demonstrated that compared to sedentary control rats, wheel running in males (Smith and Pitts 2012) and resistance training in females (Smith et al 2018) suppress heroin self-administration at the lower-end of the doseresponse curve (0.001 and 0.003 mg/kg) vs. higher unit doses. These studies suggest that exercise may reduce drug withdrawal effects and reinforcing effects of heroin and dampen reinstatement of heroin-seeking in rats.…”

Section: Introductionmentioning

confidence: 86%

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Effects of voluntary exercise and sex on multiply-triggered heroin reinstatement in male and female rats

et al. 2019

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Background-The rise in heroin addiction has heightened the need for novel and effective treatments. Physical exercise has been shown as an effective treatment for stimulant abuse in clinical and pre-clinical research. However, this treatment has not yet been tested on opioid addiction. This study examined the effects of physical activity (wheel running) on heroin-seeking in rats within a reinstatement paradigm (i.e., heroin relapse model).Methods-Female and male rats were trained to self-administer intravenous heroin (0.015 mg/ kg). Once trained, rats were placed into extinction (i.e., heroin abstinence) for 21 days with continuous access to a locked or unlocked running wheel. After extinction, rats were tested for drug-(heroin, caffeine, and yohimbine) and cue-primed reinstatement of heroin-seeking.Results-Females completed more wheel revolutions than males across all study phases. Access to an unlocked running wheel reduced extinction and reinstatement of heroin-seeking, with greater reductions in females than males across several reinstatement conditions. In the locked wheel group, female rats showed greater reinstatement of heroin-seeking than males across several priming conditions.Conclusions-Wheel running reduced heroin-seeking in male and female rats, with females showing a more robust effect during reinstatement. The locked wheel group allowed an examination of sex differences in heroin reinstatement, which revealed that females showed greater vulnerability to heroin reinstatement than males, but with no other sex differences observed in maintenance or extinction. Overall, the results indicate that voluntary physical exercise may be an effective treatment for heroin dependence in humans.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 86%

Effects of voluntary exercise and sex on multiply-triggered heroin reinstatement in male and female rats

et al. 2019

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“…Brain tissue was rapidly frozen and stored at −80 °C until further processing. RNA extraction, cDNA transcription, and RT-qPCR were performed as previously described (Smith et al 2018). Oligonucleotide primers (Table S1) were chosen from prior publications and synthesized by Invitrogen (Carlsbad, CA).…”

Section: Experiments 1 Effect Of Exercise During Abstinence On Relapsmentioning

confidence: 99%

Mechanisms underlying the efficacy of exercise as an intervention for cocaine relapse: a focus on mGlu5 in the dorsal medial prefrontal cortex

et al. 2019

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Rationale-Exercise shows promise as a treatment option for addiction, but in order to prevent relapse, it may need to be introduced early in the course of treatment. Objective-We propose that exercise, by upregulating dorsal medial prefrontal cortex (dmPFC)nucleus accumbens (NAc) transmission, offsets deficits in pathways targeting glutamate, BDNF, and dopamine during early abstinence, and in doing so, normalizes neuroadaptations that underlie relapse. Methods-We compared the effects of exercise (wheel-running, 2-hr/day) during early (days 1-7), late (days 8-14), and throughout abstinence (days 1-14) to sedentary conditions on cocaineseeking and gene expression in the dmPFC and NAc core of male rats tested following 24-hr/day extended-access cocaine (up to 96 infusions/day) or saline self-administration and protracted abstinence (15 days). Based on these data, we then used site-specific manipulation to determine whether dmPFC metabotropic glutamate receptor-5 (mGlu5) underlies the efficacy of exercise. Results-Exercise initiated during early, but not late abstinence, reduced cocaine-seeking; this effect was strongly associated with dmPFC Grm5 expression (gene encoding mGlu5), and modestly associated with dmPFC Grin1 and Bdnf-IV expression. Activation of mGlu5 in the dmPFC during early abstinence mimicked the efficacy of early-initiated exercise; however, inhibition of these receptors prior to the exercise sessions did not block its efficacy indicating that there may be redundancy in the mechanisms through which exercise reduces cocaine-seeking. Conclusion-These findings indicate that addiction treatments, including exercise, should be tailored for early versus late phases of abstinence since their effectiveness will vary over abstinence due to the dynamic nature of the underlying neuroadaptations.

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“…Resistance exercise increased mRNA expression of dopamine D5 receptors in the NAc shell and increased mRNA expression of brain-derived neurotrophic factor (exons I, IIB, IIC, IV, VI, IX) in the NAc core. Resistance exercise decreases the positive reinforcing effects of heroin and produces changes in opioid and dopamine systems in the NAc of heroinexposed rats [41].…”

Section: Discussionmentioning

confidence: 99%

Effects of circuit-type resistance training on industrial opiate induced neurotransmitter disruption and performance changes of previously addicted men

Arazi

Dadvand

2020

Biomedical Human Kinetics

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SummaryStudy aim: The aim of this study was to examine the effects of an 8-week circuit-type resistance training program on performance changes and neurotransmitter disruptions induced by industrial opiate in previously addicted men.Materials and methods: Thirty industrial opiate addicted men volunteered to participate in this study and were randomly assigned to experimental (n = 15) and control groups (n = 15). The subjects in the experimental group performed circuit-type resistance training for 8 weeks, 3 days a week, with 40–75% of one-repetition maximum (1RM), while the control group did not perform any training. Before and after the training period muscular strength (1RM of bench press) and muscle endurance (sit-ups), flexibility (sit-and-reach), body fat percentage, waist-to-hip ratio (WHR) and cardio-respiratory endurance were measured. In addition, blood samples were drawn 24 h before and after 8 weeks of training to analyze serum levels of serotonin, dopamine, and endorphins.Results: In this study, 8 weeks of circuit-type resistance training led to significantly higher serum levels of serotonin, dopamine, and endorphins, cardio-respiratory endurance, muscular strength and endurance in the experimental group compared to controls (P < 0.05), while flexibility, body fat percentage and WHR did not differ significantly (P > 0.05).Conclusions: In conclusion, circuit resistance training can improve the serum levels of serotonin, dopamine, and endorphins, as well as indicators of health-related performance previously industrial opiate addicted men.

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Resistance exercise decreases heroin self-administration and alters gene expression in the nucleus accumbens of heroin-exposed rats

Abstract: These data indicate that resistance exercise decreases the positive reinforcing effects of heroin and produces changes in opioid and dopamine systems in the NAc of heroin-exposed rats.

Cited by 24 publications

References 73 publications

Effects of voluntary exercise and sex on multiply-triggered heroin reinstatement in male and female rats

Effects of voluntary exercise and sex on multiply-triggered heroin reinstatement in male and female rats

Mechanisms underlying the efficacy of exercise as an intervention for cocaine relapse: a focus on mGlu5 in the dorsal medial prefrontal cortex

Effects of circuit-type resistance training on industrial opiate induced neurotransmitter disruption and performance changes of previously addicted men

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