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

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-s...

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Authors: Santos-Toscano, R., Arévalo, María Ángeles, García-Segura, Luis M., Grassi, Daniela, Lagunas, Natalia
Format: article
Status:Published version
Publication Date:2023
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/344874
Online Access:http://hdl.handle.net/10261/344874
Access Level:Open access
Keyword:Brain reward
Dopaminergic system
Epigenetics
Gonadal hormones
Sex differences
Substance use disorder.
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spelling Interaction of gonadal hormones, dopaminergic system, and epigenetic regulation in the generation of sex differences in substance use disorders: A systematic reviewSantos-Toscano, R.Arévalo, María ÁngelesGarcía-Segura, Luis M.Grassi, DanielaLagunas, NataliaBrain rewardDopaminergic systemEpigeneticsGonadal hormonesSex differencesSubstance use disorder.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.This work was supported by the Agencia Estatal de Investigación, Spain, and Fondo Europeo de Desarrollo Regional (FEDER) [PID2020-115019RB-I00; PID2021-125039NB-I00], Universidad Autónoma de Madrid – Comunidad Autónoma de Madrid, Programa de estímulo a la investigación de jóvenes doctores (Project SI3/PJI/2021-00508), Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid.Academic PressAgencia Estatal de Investigación (España)European CommissionUniversidad Autónoma de MadridComunidad de MadridCentro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (España)Instituto de Salud Carlos IIIConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2024202420232024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_dcae04bcPublisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/344874reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-115019RB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-125039NB-I00http://dx.doi.org/10.1016/j.yfrne.2023.101085Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3448742026-05-22T06:33:51Z
dc.title.none.fl_str_mv Interaction of gonadal hormones, dopaminergic system, and epigenetic regulation in the generation of sex differences in substance use disorders: A systematic review
title Interaction of gonadal hormones, dopaminergic system, and epigenetic regulation in the generation of sex differences in substance use disorders: A systematic review
spellingShingle Interaction of gonadal hormones, dopaminergic system, and epigenetic regulation in the generation of sex differences in substance use disorders: A systematic review
Santos-Toscano, R.
Brain reward
Dopaminergic system
Epigenetics
Gonadal hormones
Sex differences
Substance use disorder.
title_short Interaction of gonadal hormones, dopaminergic system, and epigenetic regulation in the generation of sex differences in substance use disorders: A systematic review
title_full Interaction of gonadal hormones, dopaminergic system, and epigenetic regulation in the generation of sex differences in substance use disorders: A systematic review
title_fullStr Interaction of gonadal hormones, dopaminergic system, and epigenetic regulation in the generation of sex differences in substance use disorders: A systematic review
title_full_unstemmed Interaction of gonadal hormones, dopaminergic system, and epigenetic regulation in the generation of sex differences in substance use disorders: A systematic review
title_sort Interaction of gonadal hormones, dopaminergic system, and epigenetic regulation in the generation of sex differences in substance use disorders: A systematic review
dc.creator.none.fl_str_mv Santos-Toscano, R.
Arévalo, María Ángeles
García-Segura, Luis M.
Grassi, Daniela
Lagunas, Natalia
author Santos-Toscano, R.
author_facet Santos-Toscano, R.
Arévalo, María Ángeles
García-Segura, Luis M.
Grassi, Daniela
Lagunas, Natalia
author_role author
author2 Arévalo, María Ángeles
García-Segura, Luis M.
Grassi, Daniela
Lagunas, Natalia
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación (España)
European Commission
Universidad Autónoma de Madrid
Comunidad de Madrid
Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (España)
Instituto de Salud Carlos III
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Brain reward
Dopaminergic system
Epigenetics
Gonadal hormones
Sex differences
Substance use disorder.
topic Brain reward
Dopaminergic system
Epigenetics
Gonadal hormones
Sex differences
Substance use disorder.
description 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.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_dcae04bc
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/344874
url http://hdl.handle.net/10261/344874
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-115019RB-I00
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-125039NB-I00
http://dx.doi.org/10.1016/j.yfrne.2023.101085
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Academic Press
publisher.none.fl_str_mv Academic Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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