Research Fellow, Pharmaco-Neuro-Immunology Training Program, University of Minnesota, Minneapolis, MN, USA.
Hennepin Healthcare Research Institute, Minneapolis, MN, USA.
Psychopharmacology (Berl). 2020 Feb;237(2):453-463. doi: 10.1007/s00213-019-05381-2. Epub 2019 Nov 11.
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).
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.
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.
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.
海洛因成瘾率的上升加剧了对新型有效治疗方法的需求。临床和临床前研究表明，体育锻炼是治疗兴奋剂滥用的有效方法。然而，这种治疗方法尚未在阿片类药物成瘾中进行测试。本研究在恢复模型（即海洛因复吸模型）中检验了身体活动（转轮运动）对大鼠觅药行为的影响。
雌性和雄性大鼠接受静脉注射海洛因（0.015mg/kg）的训练。一旦训练完成，大鼠被置于 21 天的消退期（即海洛因戒断），同时可连续使用上锁或不上锁的转轮。在消退期后，对大鼠进行药物（海洛因、咖啡因和育亨宾）和线索诱导的觅药行为复吸测试。
在所有研究阶段，雌性大鼠的转轮转数都多于雄性大鼠。使用不上锁的转轮可减少消退和海洛因觅药的复吸，而且在多个复吸条件下，雌性大鼠的减少程度大于雄性大鼠。在锁轮组中，与雄性大鼠相比，雌性大鼠在多个引发条件下表现出更强的海洛因觅药复吸。
转轮运动减少了雄性和雌性大鼠的海洛因觅药行为，而雌性大鼠在复吸期间表现出更强的效果。锁轮组允许对海洛因复吸的性别差异进行检查，结果表明，雌性大鼠比雄性大鼠更容易对海洛因复吸产生脆弱性，但在维持或消退期间未观察到其他性别差异。总体而言，这些结果表明，自愿进行身体锻炼可能是治疗人类海洛因依赖的有效方法。
