运动改善甲基苯丙胺戒断者抑制控制和药物渴求的机制

Mechanism by which exercise improves inhibitory control and drug craving in methamphetamine abstinent patients

背景:抑制控制和药物渴求是评估甲基苯丙胺成瘾者药物戒断的核心要素,备受学界关注。众所周知,要彻底实现对药物成瘾的戒断,恢复吸毒者受损的抑制控制功能,有效降低对药物的渴求是关键。目的:旨在通过系统分析运动与甲基苯丙胺戒断者抑制控制和药物渴求的关系,找出促进甲基苯丙胺成瘾戒断的有效运动干预方案,并进一步探究运动作用的内在机制,以期为未来运动运用于毒品戒断提供理论上的支持和应用上的参考。方法:通过检索中国知网、万方、维普、Web of Science及PubMed数据库,中文检索词为“运动,体育锻炼,甲基苯丙胺,抑制功能,渴求度,成瘾”等,英文检索词为“Sport*,Exercise,Methamphetamine,Drug craving,Executive function,Addiction”等,依据纳入和排除标准对文献进行筛选,最终获得目标文献65篇进行综述分析。结果与结论:①运动对甲基苯丙胺戒断者抑制控制方面,急性和长期中等强度有氧运动或急性中高强度间歇训练均能够显著提升甲基苯丙胺戒断者抑制控制能力,对于长期有氧运动而言,有氧操课练习或全身性的综合练习效果更佳,若运动形式为功率自行车,建议增加运动干预频次。②运动对甲基苯丙戒断者药物渴求度方面,急性中等强度有氧运动和抗阻力训练或长期中等强度、高强度或递增负荷的有氧及抗阻力训练均能够有效降低甲基苯丙胺戒断者的药物渴求度。③运动对甲基苯丙胺介导的机体成瘾具有内在调控作用,首先,运动可通过影响大脑腹侧被盖区酪氨酸羟化酶的表达,进而刺激多巴胺受体偶联蛋白的表达,促进大脑奖赏区域多巴胺的合成,弥补由于甲基苯丙胺成瘾导致的多巴胺耗竭;其次,运动也可通过调控蛋白激酶A抑制剂,影响多巴胺D1受体介导的蛋白激酶A信号通路,通过抑制蛋白激酶A从而影响环磷酸腺苷反应结合蛋白,实现对甲基苯丙胺成瘾的调控;最后,运动也可在基因水平上通过影响大脑红核区细胞c-fos基因的表达,激活该区域谷氨酸神经元亚群,产生奖赏效应,实现对甲基苯丙胺成瘾的改善。④虽然目前研究已证实运动与甲基苯丙胺成瘾的关系,且已明晰运动作用的脑内机制,但是否还存在运动作用的其他脑内调控途径有待通过设计更为科学、严谨的动物或人体实验,从细胞或分子学水平出发进行深入探究。

BACKGROUND:Inhibitory control and drug craving are the core elements of evaluating drug withdrawal in methamphetamine addicts,which has attracted much attention in academic circles.As we all know,in order to achieve complete abstinence from drug addiction,the key is to restore the damaged inhibition and control function of drug addicts and effectively reduce the craving for drugs.OBJECTIVE:To systematically analyze the relationship between exercise and methamphetamine abstinence inhibitory control and drug craving,to find out an effective exercise intervention scheme that can promote methamphetamine abstinence,and to further explore the internal mechanism of exercise,in order to provide theoretical support and applied reference for the future use of exercise in drug withdrawal.METHODS:CNKI,WanFang,VIP,Web of Science,and PubMed databases were searched for relevant literature using the keywords of“exercise,physical activity,methamphetamine,inhibitory function,craving,addiction”in Chinese and“sport*,exercise,methamphetamine,drug craving,executive function,addiction”in English.According to the inclusion and exclusion criteria,86 documents were finally included for review.RESULTS AND CONCLUSION:In terms of inhibitory control in methamphetamine abstinent individuals,either acute and long-term moderate-intensity aerobic exercise or acute high-intensity interval training can significantly improve the inhibitory control capacity of methamphetamine abstinent individuals.For long-term aerobic exercise,aerobic group exercise or full-body comprehensive exercise is more effective.If the exercise format is power cycling,it is recommended to increase the frequency of exercise intervention.In terms of the drug craving intensity in methamphetamine abstinent individuals,acute moderate-intensity aerobic exercise and resistance training,as well as long-term moderate-intensity,high-intensity,or progressive load aerobic and resistance training,can effectively reduce the drug craving in methamphetamine abstinent individuals.Exercise exerts intrinsic regulatory effects on methamphetamine-mediated addiction.Exercise can influence the expression of tyrosine hydroxylase in the brain’s ventral tegmental area,thereby stimulating the expression of dopamine receptor coupling proteins and promoting dopamine synthesis in the brain’s reward regions,thereby compensating for dopamine depletion caused by methamphetamine addiction.Furthermore,exercise can also regulate protein kinase A inhibitors,affecting the protein kinase A signaling pathway mediated by dopamine D1 receptors,by inhibiting protein kinase A,thus affecting cAMP response element-binding protein and regulating methamphetamine addiction.Additionally,exercise can also,at the genetic level,affect the expression of the c-fos gene in the brain’s nucleus accumbens region,activate a subset of glutamatergic neurons in this area,generate a rewarding effect,and thus improve methamphetamine addiction.Although current research has confirmed the relationship between exercise and methamphetamine addiction and has clarified the brain mechanisms underlying the effects of exercise,whether there are other brain regulatory pathways for the effects of exercise remains to be explored through more scientifically rigorous animal or human experiments,starting from the cellular or molecular level.