Advertisement

Current Addiction Reports

, Volume 4, Issue 4, pp 455–466 | Cite as

Exercise as a Prevention for Substance Use Disorder: a Review of Sex Differences and Neurobiological Mechanisms

  • Wendy J. Lynch
  • Andrea M. Robinson
  • Jean Abel
  • Mark A. Smith
Women and Addictions (CM Mazure and Y Zakiniaeiz, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Women and Addictions

Abstract

Purpose of Review

This report provides an update on clinical and preclinical findings for the efficacy of exercise to prevent substance use disorder with a focus on recent evidence for sex differences and neurobiological mechanisms.

Recent Findings

Exercise/physical activity is associated with decreased drug use in humans. Preclinical results further indicate that exercise decreases vulnerability to drug use and the development of features of substance use disorder, and suggest that females have an enhanced sensitivity to its reward-substitution effects. However, certain exercise conditions may sensitize the reward pathway and enhance vulnerability suggesting that parallel observations in humans (e.g., increased prescription opioid misuse and heroin use in high-school athletes) may be biologically based.

Summary

Exercise is a promising prevention strategy for substance use disorder. Further work is needed to establish its efficacy as a sex-specific strategy using larger samples and to understand the exercise conditions that induce beneficial versus risk-enhancing effects.

Keywords

Acquisition Addiction Animal models Biological mechanisms Clinical Drug use initiation Drug use escalation Exercise Gender differences Gonadal hormones Intervention Physical activity Preclinical Prevention Sex differences Sex-specific Substance use disorder 

Notes

Funding Information

Wendy J Lynch is supported by grants from National Institute on Drug Abuse (grants no. R01DA024716 and R01DA039093). Mark A. Smith is supported by a grant from the National Institute on Drug Abuse (grant no. DA031725).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Greer TL, Ring KM, Warden D, Grannemann BD, Church TS, Somoza E, Blair SN, Szapocznik J, Stoutenberg M, Rethorst C, Walker R, Morris DW, Kosinski AS, Kyle T, Marcus B, Crowell B, Oden N, Nunes E, Trivedi MH. Rationale for using exercise in the treatment of stimulant use disorders. J Glob Drug Policy Pract. 2012;6(1).Google Scholar
  2. 2.
    Linke SE, Ussher M. Exercise-based treatments for substance use disorders: evidence, theory, and practicality. Am J Drug Alcohol Abuse. 2015;41(1):7–15.PubMedCrossRefGoogle Scholar
  3. 3.
    Tuchman E. Women and addiction: the importance of gender issues in substance abuse research. J Addict Dis. 2010;29(2):127–38.PubMedCrossRefGoogle Scholar
  4. 4.
    Hamřík Z, Bobáková D, Kalman M, Veselská ZD, Klein D, Gecková AM. Physical activity and screen-based activity in healthy development of school-aged children. Cent Eur J Public Health. 2015;23(Suppl):S50–6.PubMedGoogle Scholar
  5. 5.
    Henchoz Y, Dupuis M, Deline S, Studer J, Baggio S, N’Goran AA, et al. Associations of physical activity and sport and exercise with at-risk substance use in young men: a longitudinal study. Prev Med. 2014;64:27–31.PubMedCrossRefGoogle Scholar
  6. 6.
    Lesjak V, Stanojević-Jerković O. Physical activity, sedentary behavior and substance use among adolescents in Slovenian urban area. Zdr Varst. 2015;54(3):168–74.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Tabak I, Mazur J, Zawadzka D. Physical activity as a factor protecting teenage boys from tobacco and marihuana use. Przegl Epidemio. 2015;69(4):795-800–19-22.Google Scholar
  8. 8.
    Sanchez V, Lycas MD, Lynch WJ, Brunzell DH. Wheel running exercise attenuates vulnerability to self-administer nicotine in rats. Drug Alcohol Depend. 2015;156:193–8.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    • Engelmann AJ, Aparicio MB, Kim A, Sobieraj JC, Yuan CJ, Grant Y, et al. Chronic wheel running reduces maladaptive patterns of methamphetamine intake: regulation by attenuation of methamphetamine-induced neuronal nitric oxide synthase. Brain Struct Funct. 2014;219(2):657–72. This study showed that terminating exercise sessions prior to methamphetamine self-administration training enhanced rates of acquisition in rats that had a history of unlimited voluntary wheel running indicating that certain exercise conditions enhance vulnerability to drugs of abuse. PubMedCrossRefGoogle Scholar
  10. 10.
    Lynch WJ, Abel J, Robinson AM, Smith MA. Part II: exercise as a treatment for substance use disorder: a review of sex differences and neurobiological mechanisms. Curr Addict Reports, (2017) In Press.Google Scholar
  11. 11.
    Zhou Y, Zhao M, Zhou C, Li R. Sex differences in drug addiction and response to exercise intervention: from human to animal studies. Front Neuroendocrinol. 2016;40:24–41.PubMedCrossRefGoogle Scholar
  12. 12.
    • Veliz P, Boyd CJ, McCabe SE. Nonmedical use of prescription opioids and heroin use among adolescents involved in competitive sports. J Adolesc Health. 2017;60(3):346–9. This study showed high-school participation in certain sports where risk of injury is high (e.g., football, ice hockey, lacrosse, and wrestling) and is associated with increased prescription opioid misuse and heroin. PubMedCrossRefGoogle Scholar
  13. 13.
    Veliz P, Epstein-Ngo QM, Meier E, Ross-Durow PL, McCabe SE, Boyd CJ. Painfully obvious: a longitudinal examination of medical use and misuse of opioid medication among adolescent sports participants. J Adolesc Health. 2014;54(3):333–40.PubMedCrossRefGoogle Scholar
  14. 14.
    Fujimoto K, Unger JB, Valente TW. A network method of measuring affiliation-based peer influence: assessing the influences of teammates’ smoking on adolescent smoking. Child Dev. 2012;83(2):442–51.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Kwan M, Bobko S, Faulkner G, Donnelly P, Cairney J. Sport participation and alcohol and illicit drug use in adolescents and young adults: a systematic review of longitudinal studies. Addict Behav. 2014;39(3):497–506.PubMedCrossRefGoogle Scholar
  16. 16.
    Terry-McElrath YM, O’Malley PM, Johnston LD. Exercise and substance use among American youth, 1991-2009. Am J Prev Med. 2011;40(5):530–40.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Lynch WJ, Peterson AB, Sanchez V, Abel J, Smith MA. Exercise as a novel treatment for drug addiction: a neurobiological and stage-dependent hypothesis. Neurosci Biobehav Rev. 2013;37(8):1622–44.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Gray KM, Squeglia LM. What have we learned about adolescent substance use? J Child Psychol Psychiatry. 2017.  https://doi.org/10.1111/jcpp.12783.
  19. 19.
    Stone AL, Becker LG, Huber AM, Catalano RF. Review of risk and protective factors of substance use and problem use in emerging adulthood. Addict Behav. 2012;37(7):747–75.PubMedCrossRefGoogle Scholar
  20. 20.
    Lisha NE, Crano WD, Delucchi KL. Participation in team sports and alcohol and marijuana use initiation trajectories. J Drug Issues. 2014;44(1):83–93.PubMedCrossRefGoogle Scholar
  21. 21.
    Mattila VM, Raisamo S, Pihlajamäki H, Mäntysaari M, Rimpelä A. Sports activity and the use of cigarettes and snus among young males in Finland in 1999-2010. BMC Public Health. 2012;12:230.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Veliz PT, Boyd C, McCabe SE. Playing through pain: sports participation and nonmedical use of opioid medications among adolescents. Am J Public Health. 2013;103(5):e28–30.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Veliz P, Schulenberg J, Patrick M, Kloska D, McCabe SE, Zarrett N. Competitive sports participation in high school and subsequent substance use in young adulthood: assessing differences based on level of contact. Int Rev Sociol Sport. 2017;52(2):240–59.PubMedCrossRefGoogle Scholar
  24. 24.
    Veliz P, McCabe SE. Examining potential substance use disorders among former interscholastic athletes. Subst Abus. 2015;36(4):400–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Veliz P, Boyd CJ, McCabe SE. Nonmedical prescription opioid and heroin use among adolescents who engage in sports and exercise. Pediatrics. 2016;138(2)  https://doi.org/10.1542/peds.2016-0677.
  26. 26.
    Martinsen M, Sundgot-Borgen J. Adolescent elite athletes’ cigarette smoking, use of snus, and alcohol. Scand J Med Sci Sports. 2014;24(2):439–46.PubMedCrossRefGoogle Scholar
  27. 27.
    Velicer WF, Redding CA, Paiva AL, Mauriello LM, Blissmer B, Oatley K, et al. Multiple behavior interventions to prevent substance abuse and increase energy balance behaviors in middle school students. Transl Behav Med. 2013;3(1):82–93.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Weinstock J, Capizzi J, Weber SM, Pescatello LS, Petry NM. Exercise as an intervention for sedentary hazardous drinking college students: a pilot study. Ment Health Phys Act. 2014;7(1):55–62.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Varì R, Scazzocchio B, D’Amore A, Giovannini C, Gessani S, Masella R. Gender-related differences in lifestyle may affect health status. Ann Ist Super Sanita. 2016;52(2):158–66.PubMedGoogle Scholar
  30. 30.
    Hebert JJ, Møller NC, Andersen LB, Wedderkopp N. Organized sport participation is associated with higher levels of overall health-related physical activity in children (CHAMPS Study-DK). PLoS One. 2015;10(8):e0134621.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    World Health Organization. Global recommendations on physical activity for health. Geneva: World Health Organization; 2010. Report No.: 9789241599979Google Scholar
  32. 32.
    Lisha NE, Sussman S. Relationship of high school and college sports participation with alcohol, tobacco, and illicit drug use: a review. Addict Behav. 2010;35(5):399–407.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Publishing; 2013.CrossRefGoogle Scholar
  34. 34.
    Miller ML, Vaillancourt BD, Wright MJ Jr, Aarde SM, Vandewater SA, Creehan KM, et al. Reciprocal inhibitory effects of intravenous d-methamphetamine self-administration and wheel activity in rats. Drug Alcohol Depend. 2012;121(1–2):90–6.PubMedCrossRefGoogle Scholar
  35. 35.
    Smith MA, Fronk GE, Zhang H, Magee CP, Robinson AM. Acute bouts of wheel running decrease cocaine self-administration: influence of exercise output. Pharmacol Biochem Behav. 2016;150-151:94–9.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Strickland JC, Abel JM, Lacy RT, Beckmann JS, Witte MA, Lynch WJ, et al. The effects of resistance exercise on cocaine self-administration, muscle hypertrophy, and BDNF expression in the nucleus accumbens. Drug Alcohol Depend. 2016;163:186–94.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Brager AJ, Hammer SB. Impact of wheel running on chronic ethanol intake in aged Syrian hamsters. Physiol Behav. 2012;107(3):418–23.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Darlington TM, McCarthy RD, Cox RJ, Miyamoto-Ditmon J, Gallego X, Ehringer MA. Voluntary wheel running reduces voluntary consumption of ethanol in mice: identification of candidate genes through striatal gene expression profiling. Genes Brain Behav. 2016;15(5):474–90.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Gallego X, Cox RJ, Funk E, Foster RA, Ehringer MA. Voluntary exercise decreases ethanol preference and consumption in C57BL/6 adolescent mice: sex differences and hippocampal BDNF expression. Physiol Behav. 2015;138:28–36.PubMedCrossRefGoogle Scholar
  40. 40.
    Lacy RT, Strickland JC, Brophy MK, Witte MA, Smith MA. Exercise decreases speedball self-administration. Life Sci. 2014;114(2):86–92.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Smith MA, Pitts EG. Wheel running decreases the positive reinforcing effects of heroin. Pharmacol Rep. 2012;64(4):960–4.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Smith MA, Witte MA. The effects of exercise on cocaine self-administration, food-maintained responding, and locomotor activity in female rats: importance of the temporal relationship between physical activity and initial drug exposure. Exp Clin Psychopharmacol. 2012;20(6):437–46.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Aarde SM, Miller ML, Creehan KM, Vandewater SA, Taffe MA. One day access to a running wheel reduces self-administration of D-methamphetamine, MDMA and methylone. Drug Alcohol Depend. 2015;151:151–8.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Zlebnik NE, Anker JJ, Carroll ME. Exercise to reduce the escalation of cocaine self-administration in adolescent and adult rats. Psychopharmacology. 2012;224(3):387–400.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Eisenstein SA, Holmes PV. Chronic and voluntary exercise enhances learning of conditioned place preference to morphine in rats. Pharmacol Biochem Behav. 2007;86(4):607–15.PubMedCrossRefGoogle Scholar
  46. 46.
    Smith MA, Gergans SR, Iordanou JC, Lyle MA. Chronic exercise increases sensitivity to the conditioned rewarding effects of cocaine. Pharmacol Rep. 2008;60(4):561–5.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Smith MA, Walker KL, Cole KT, Lang KC. The effects of aerobic exercise on cocaine self-administration in male and female rats. Psychopharmacology. 2011;218(2):357–69.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Cosgrove KP, Hunter RG, Carroll ME. Wheel-running attenuates intravenous cocaine self-administration in rats: sex differences. Pharmacol Biochem Behav. 2002;73(3):663–71.PubMedCrossRefGoogle Scholar
  49. 49.
    Carroll ME, Smethells JR. Sex differences in behavioral dyscontrol: role in drug addiction and novel treatments. Front Psychiatry. 2016;6:175.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Anantharaman-Barr HG, Decombaz J. The effect of wheel running and the estrous cycle on energy expenditure in female rats. Physiol Behav. 1989;46(2):259–63.PubMedCrossRefGoogle Scholar
  51. 51.
    Carroll ME, Lynch WJ. How to study sex differences in addiction using animal models. Addict Biol. 2016;21(5):1007–29.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Di Chiara G, Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci. 1988;85(14):5274–8.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Greenwood BN, Foley TE, Le TV, Strong PV, Loughridge AB, Day HE, et al. Long-term voluntary wheel running is rewarding and produces plasticity in the mesolimbic reward pathway. Behav Brain Res. 2011;217(2):354–62.PubMedCrossRefGoogle Scholar
  54. 54.
    Herrera JJ, Fedynska S, Ghasem PR, Wieman T, Clark PJ, Gray N, et al. Neurochemical and behavioural indices of exercise reward are independent of exercise controllability. Eur J Neurosci. 2016;43(9):1190–202.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Singer G, Wallace M. Effects of 6-OHDA lesions in the nucleus accumbens on the acquisition of self injection of heroin under schedule and non schedule conditions in rats. Pharmacol Biochem Behav. 1984;20(5):807–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Basso JC, Morrell JI. The medial prefrontal cortex and nucleus accumbens mediate the motivation for voluntary wheel running in the rat. Behav Neurosci. 2015;129(4):457–72.PubMedCrossRefGoogle Scholar
  57. 57.
    Ashok AH, Mizuno Y, Volkow ND, Howes OD. Association of stimulant use with dopaminergic alterations in users of cocaine, amphetamine, or methamphetamine: a systematic review and meta-analysis. JAMA Psychiatry. 2017;74(5):511–9.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Park YM, Kanaley JA, Padilla J, Zidon T, Welly RJ, Will MJ, et al. Effects of intrinsic aerobic capacity and ovariectomy on voluntary wheel running and nucleus accumbens dopamine receptor gene expression. Physiol Behav. 2016;164(Pt A):383–9.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Zlebnik NE, Hedges VL, Carroll ME, Meisel RL. Chronic wheel running affects cocaine-induced c-Fos expression in brain reward areas in rats. Behav Brain Res. 2014;261:71–8.PubMedCrossRefGoogle Scholar
  60. 60.
    Chen W, Wang HJ, Shang NN, Liu J, Li J, Tang DH, et al. Moderate intensity treadmill exercise alters food preference via dopaminergic plasticity of ventral tegmental area-nucleus accumbens in obese mice. Neurosci Lett. 2017;641:56–61.PubMedCrossRefGoogle Scholar
  61. 61.
    Obici S, Magrisso IJ, Ghazarian AS, Shirazian A, Miller JR, Loyd CM, et al. Moderate voluntary exercise attenuates the metabolic syndrome in melanocortin-4 receptor-deficient rats showing central dopaminergic dysregulation. Mol Metab. 2015;4(10):692–705.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Toy WA, Petzinger GM, Leyshon BJ, Akopian GK, Walsh JP, Hoffman MV, et al. Treadmill exercise reverses dendritic spine loss in direct and indirect striatal medium spiny neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. Neurobiol Dis. 2014;63:201–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Chen HI, Kuo YM, Liao CH, Jen CJ, Huang AM, Cherng CG, et al. Long-term compulsive exercise reduces the rewarding efficacy of 3,4-methylenedioxymethamphetamine. Behav Brain Res. 2008;187(1):185–9.PubMedCrossRefGoogle Scholar
  64. 64.
    Garcia PC, Real CC, Britto LR. The impact of short and long-term exercise on the expression of Arc and AMPARs during evolution of the 6-hydroxy-dopamine animal model of Parkinson’s disease. J Mol Neurosci. 2017;61(4):542–52.PubMedCrossRefGoogle Scholar
  65. 65.
    Edwards S, Koob GF. Escalation of drug self-administration as a hallmark of persistent addiction liability. Behav Pharmacol. 2013;24(5–6):356–62.PubMedCrossRefGoogle Scholar
  66. 66.
    Abel JL, Rissman EF. Running-induced epigenetic and gene expression changes in the adolescent brain. Int J Dev Neurosci. 2013;31(6):382–90.PubMedCrossRefGoogle Scholar
  67. 67.
    Pierce RC, Vassoler FM. Reduced cocaine reinforcement in the male offspring of cocaine-experienced sires. Neuropsychopharmacology. 2014;39(1):238.PubMedCrossRefGoogle Scholar
  68. 68.
    Zoladz JA, Pilc A. The effect of physical activity on the brain derived neurotrophic factor: from animal to human studies. J Physiol Pharmacol. 2010;61(5):533–41.PubMedGoogle Scholar
  69. 69.
    Xu X, Ji H, Liu G, Wang Q, Liu H, Shen W, et al. A significant association between BDNF promoter methylation and the risk of drug addiction. Gene. 2016;584(1):54–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Yoest KE, Cummings JA, Becker JB. Estradiol, dopamine and motivation. Cent Nerv Syst Agents Med Chem. 2014;14(2):83–9.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Befort K. Interactions of the opioid and cannabinoid systems in reward: insights from knockout studies. Front Pharmacol. 2015;6:6.PubMedPubMedCentralGoogle Scholar
  72. 72.
    Roberts MD, Ruegsegger GN, Brown JD, Booth FW. Mechanisms associated with physical activity behavior: insights from rodent experiments. Exerc Sport Sci Rev. 2017;45(4):217–222.Google Scholar
  73. 73.
    Telford RM, Telford RD, Olive LS, Cochrane T, Davey R. Why are girls less physically active than boys? Findings from the LOOK Longitudinal Study. PLoS One. 2016;11(3):e0150041.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Dumith SC, Gigante DP, Domingues MR, Kohl HW 3rd. Physical activity change during adolescence: a systematic review and a pooled analysis. Int J Epidemiol. 2011;40(3):685–98.PubMedCrossRefGoogle Scholar
  75. 75.
    Horn K, Dino G, Branstetter SA, Zhang J, Noerachmanto N, Jarrett T, et al. Effects of physical activity on teen smoking cessation. Pediatrics. 2011;128(4):e801–11.PubMedCrossRefGoogle Scholar
  76. 76.
    Paukste E, Harris N. Using rap music to promote adolescent health: pilot study of VoxBox. Health Promot J Austr. 2015;26(1):24-6–8-9.Google Scholar
  77. 77.
    Schaus JF, Sole ML, McCoy TP, Mullett N, O’Brien MC. Alcohol screening and brief intervention in a college student health center: a randomized controlled trial. J Stud Alcohol Drugs Suppl. 2009;(16):131–41.Google Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Wendy J. Lynch
    • 1
  • Andrea M. Robinson
    • 2
  • Jean Abel
    • 1
  • Mark A. Smith
    • 2
  1. 1.University of VirginiaCharlottesvilleUSA
  2. 2.Davidson CollegeDavidsonUSA

Personalised recommendations