Neurocentre Magendie, University of Bordeaux, Bordeaux, France (C.N.); Department of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD, Present address: Division of Biomedical Sciences, University of California Riverside, School of Medicine, Riverside, CA (N.E.Z.); Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD (M.F., L.L., S.I., Y.S.); and Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD (M.F., L.L.)
Neurocentre Magendie, University of Bordeaux, Bordeaux, France (C.N.); Department of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD, Present address: Division of Biomedical Sciences, University of California Riverside, School of Medicine, Riverside, CA (N.E.Z.); Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD (M.F., L.L., S.I., Y.S.); and Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD (M.F., L.L.).
Pharmacol Rev. 2022 Jan;74(1):119-140. doi: 10.1124/pharmrev.121.000367.
A widely held dogma in the preclinical addiction field is that females are more vulnerable than males to drug craving and relapse. Here, we first review clinical studies on sex differences in psychostimulant and opioid craving and relapse. Next, we review preclinical studies on sex differences in psychostimulant and opioid reinstatement of drug seeking after extinction of drug self-administration, and incubation of drug craving (time-dependent increase in drug seeking during abstinence). We also discuss ovarian hormones' role in relapse and craving in humans and animal models and speculate on brain mechanisms underlying their role in cocaine craving and relapse in rodent models. Finally, we discuss imaging studies on brain responses to cocaine cues and stress in men and women.The results of the clinical studies reviewed do not appear to support the notion that women are more vulnerable to psychostimulant and opioid craving and relapse. However, this conclusion is tentative because most of the studies reviewed were correlational, not sufficiently powered, and not a priori designed to detect sex differences. Additionally, imaging studies suggest sex differences in brain responses to cocaine cues and stress. The results of the preclinical studies reviewed provide evidence for sex differences in stress-induced reinstatement and incubation of cocaine craving but not cue- or cocaine-induced reinstatement of cocaine seeking. These sex differences are modulated in part by ovarian hormones. In contrast, the available data do not support the notion of sex differences in craving and relapse/reinstatement for methamphetamine or opioids in rodent models. SIGNIFICANCE STATEMENT: This systematic review summarizes clinical and preclinical studies on sex differences in psychostimulant and opioid craving and relapse. Results of the clinical studies reviewed do not appear to support the notion that women are more vulnerable to psychostimulant and opioid craving and relapse. Results of preclinical studies reviewed provide evidence for sex differences in reinstatement and incubation of cocaine seeking but not for reinstatement or incubation of methamphetamine or opioid seeking.
在临床前成瘾领域，一个普遍存在的观点是，女性比男性更容易产生药物渴求并复吸。在这里，我们首先回顾了关于精神兴奋剂和阿片类药物渴求与复吸的性别差异的临床研究。接下来，我们回顾了关于精神兴奋剂和阿片类药物在药物自我给药消退后药物寻求的复吸和渴求潜伏期（禁欲期间药物寻求的时间依赖性增加）的性别差异的临床前研究。我们还讨论了卵巢激素在人类和动物模型中的复吸和渴求中的作用，并推测了其在啮齿动物模型中可卡因渴求和复吸中的作用的大脑机制。最后，我们讨论了关于男性和女性对可卡因线索和压力的大脑反应的影像学研究。所回顾的临床研究的结果似乎并不支持女性更容易产生精神兴奋剂和阿片类药物渴求与复吸的观点。然而，由于大多数综述研究是相关的，没有足够的效力，也不是预先设计来检测性别差异，因此这个结论是暂定的。此外，影像学研究表明，大脑对可卡因线索和压力的反应存在性别差异。所回顾的临床前研究的结果提供了证据表明，应激诱导的可卡因渴求复吸和潜伏期存在性别差异，但可卡因线索或可卡因诱导的可卡因寻求复吸没有性别差异。这些性别差异部分受到卵巢激素的调节。相比之下，现有的数据并不支持在啮齿动物模型中存在与性别的差异的关于甲基苯丙胺或阿片类药物的渴求与复吸/复燃的观点。意义陈述：本系统综述总结了关于精神兴奋剂和阿片类药物渴求与复吸的性别差异的临床和临床前研究。所回顾的临床研究的结果似乎并不支持女性比男性更容易产生药物渴求与复吸的观点。所回顾的临床前研究的结果提供了证据表明，在可卡因寻求的复吸和潜伏期方面存在性别差异，但在甲基苯丙胺或阿片类药物寻求的复吸或潜伏期方面没有性别差异。
