Sex differences in vulnerability to drug self-administration
Sex differences in vulnerability to drug self-administration
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DOI：
10.1037/1064-1297.14.1.34
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发表时间：
2006-02-01
影响因子：
2.3
通讯作者：
Lynch, WJ
中科院分区：
文献类型：
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作者：
Lynch, WJ
来自人类和动物研究的最新证据表明，在成瘾过程的所有阶段都存在性别差异，包括开始和获得使用，使用模式和水平，成瘾进展和复发。本文简要总结了一系列关于大鼠自我给药的性别差异的研究，并将这些研究结果与人类临床数据联系起来，这些研究是惠氏杨精神药理学家奖的基础。简而言之，临床前研究结果表明，与雄性大鼠相比，雌性大鼠获得药物自我给药的速度更快，更努力地获得药物输注，“暴食”的初始时间更长，在扩展获取条件下表现出更严重的每日自我给药失调模式，并且在恢复测试条件下的反应水平更高。类似的结果在人类身上也有报道，这表明对药物滥用的脆弱性存在性别差异的生物学基础。许多生物学机制已经被探索，结果表明卵巢激素在调节女性药物滥用的强化效应中起着关键作用。临床前研究与人体研究相结合，应进一步为药物滥用差异的性别特异性模型提供信息，这种模型可能有助于制定药物滥用的预防和治疗战略。
Recent evidence from both human and animal studies indicates that there are sex differences in all phases of the addiction process, including initiation and acquisition of use, patterns and levels of use, the progression to addiction, and relapse. This brief review summarizes a series of studies on sex differences in drug self-administration in rats on which the Wyeth Young Psychopharmacologist Award was based and relates these findings to human clinical data. Briefly, preclinical findings show that female rats acquire drug self-administration at a faster rate, work harder to obtain drug infusions, "binge" for longer initial periods of time and show a more diurnally dysregulated pattern of self-administration under extended-access conditions, and respond at higher levels under reinstatement testing conditions compared with male rats. Similar results have been reported in humans, suggesting a biological basis of sex differences in vulnerability to drug abuse. A number of biological mechanisms have been explored, and the results show that ovarian hormones play a critical role in modulating the reinforcing effects of drugs of abuse in females. Preclinical studies, in conjunction with human studies, should further inform a sex-specific model for differences in drug abuse, and such a model may be useful for developing prevention and treatment strategies for drug abuse.