Interaction of gonadal hormones, dopaminergic system, and epigenetic regulation in the generation of sex differences in substance use disorders: A systematic review

IF 6.5 1区医学 Q1 ENDOCRINOLOGY & METABOLISM Frontiers in Neuroendocrinology Pub Date : 2023-10-01 DOI:10.1016/j.yfrne.2023.101085

Raquel Santos-Toscano , Maria Angeles Arevalo , Luis Miguel Garcia-Segura , Daniela Grassi , Natalia Lagunas

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Abstract

Substance use disorder (SUD) is a chronic condition characterized by pathological drug-taking and seeking behaviors. Remarkably different between males and females, suggesting that drug addiction is a sexually differentiated disorder. The neurobiological bases of sex differences in SUD include sex-specific reward system activation, influenced by interactions between gonadal hormone level changes, dopaminergic reward circuits, and epigenetic modifications of key reward system genes. This systematic review, adhering to PICOS and PRISMA-P 2015 guidelines, highlights the sex-dependent roles of estrogens, progesterone, and testosterone in SUD. In particular, estradiol elevates and progesterone reduces dopaminergic activity in SUD females, whilst testosterone and progesterone augment SUD behavior in males. Finally, SUD is associated with a sex-specific increase in the rate of opioid and monoaminergic gene methylation. The study reveals the need for detailed research on gonadal hormone levels, dopaminergic or reward system activity, and epigenetic landscapes in both sexes for efficient SUD therapy development.

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性腺激素、多巴胺能系统和表观遗传调控在物质使用障碍性别差异产生中的相互作用:系统综述

物质使用障碍（SUD）是一种以病理性服药和寻求行为为特征的慢性疾病。男性和女性之间存在显著差异，这表明毒瘾是一种性别分化障碍。SUD性别差异的神经生物学基础包括性别特异性奖励系统激活，受性腺激素水平变化、多巴胺能奖励回路和关键奖励系统基因表观遗传修饰之间相互作用的影响。这篇系统综述遵循PICOS和PRISMA-P 2015指南，强调了雌激素、孕酮和睾酮在SUD中的性别依赖性作用。特别是，雌二醇升高和孕酮降低SUD女性的多巴胺能活性，而睾酮和孕酮增强男性的SUD行为。最后，SUD与阿片类药物和单胺能基因甲基化率的性别特异性增加有关。这项研究表明，需要对两性的性腺激素水平、多巴胺能或奖赏系统活性以及表观遗传学景观进行详细研究，以开发有效的SUD疗法。

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来源期刊

Frontiers in Neuroendocrinology 医学-内分泌学与代谢

CiteScore

13.30

自引率

6.80%

发文量

审稿时长

68 days

期刊介绍： Frontiers in Neuroendocrinology (FIN) publishes a wide range of informative articles including comprehensive reviews, systematic reviews, opinion pieces, and meta-analyses. While the majority of reviews are invited, we also embrace unsolicited reviews and meta-analyses, as well as proposals for thematic special issues, provided they meet our rigorous quality standards. In addition, we encourage authors to submit commentaries that concisely present fresh ideas or offer further analysis to delve deeper into the implications of an article published in our journal.