Sex differences and ovarian hormones in animal models of drug dependence

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145 Scopus citations

Abstract

Increasing evidence indicates the presence of sex differences in many aspects of drug abuse. Most studies reveal that females exceed males during the initiation, escalation, extinction, and reinstatement (relapse) of drug-seeking behavior, but males are more sensitive than females to the aversive effects of drugs such as drug withdrawal. Findings from human and animal research indicate that circulating levels of ovarian steroid hormones account for these sex differences. Estrogen (E) facilitates drug-seeking behavior, while progesterone (P) and its metabolite, allopregnanalone (ALLO), counteract the effects of E and reduce drug seeking. Estrogen and P influence other behaviors that are affiliated with drug abuse such as drug-induced locomotor sensitization and conditioned place preference. The enhanced vulnerability to drug seeking in females vs. males is also additive with the other risk factors for drug abuse (e.g., adolescence, sweet preference, novelty reactivity, and impulsivity). Finally, treatment studies using behavioral or pharmacological interventions, including P and ALLO, also indicate that females show greater treatment effectiveness during several phases of the addiction process. The neurobiological basis of sex differences in drug abuse appears to be genetic and involves the influence of ovarian hormones and their metabolites, the hypothalamic pituitary adrenal (HPA) axis, dopamine (DA), and gamma-hydroxy-butyric acid (GABA). Overall, sex and hormonal status along with other biological risk factors account for a continuum of addiction-prone and -resistant animal models that are valuable for studying drug abuse prevention and treatment strategies.

Original languageEnglish (US)
Pages (from-to)44-56
Number of pages13
JournalHormones and Behavior
Volume58
Issue number1
DOIs
StatePublished - Jun 2010

Bibliographical note

Funding Information:
The authors are grateful to Drs. Erin Larson, Jennifer Newman, and Jennifer Perry for conducting some of the research reported here during their pre- (EL, JP) and post-doctoral (JN) training, and to Luke Gliddon, Nathan Holtz, Emily Kidd, Rachel LaNasa, Jami Mach, Amy Saykao, Matt Starr, Rachael Turner, and Natalie Zlebnik for their expert assistance in data collection and analysis on studies that were reviewed in this article. We also appreciate the grant support of the National Institute on Drug Abuse , R01 DA003240-26 , R01 DA002486-29 , R01 DA 019942-02 , P20 DA024196-02 , K05 DA015267-08 (MEC) and F31 DA 023301-02 (JJA).

Keywords

  • Animal models
  • Aversive effects
  • Drug dependence
  • Neurobiological basis
  • Ovarian steroid hormones
  • Phases of addiction
  • Sex differences
  • Stress hormonal interactions

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