Ovarian Hormones and Addictive Behaviour Vulnerability: Insights From Preclinical Studies

ABSTRACT Substance use disorder constitutes a global health challenge. Preclinical investigations into addiction heavily rely on animal models to explore the underlying biological mechanisms of addictive disorders, with a particular emphasis on understanding the etiological factors influencing drug intake. Exploring sex differences across various phases of addiction has revealed a heightened vulnerability in females. This study systematically reviews the impact of ovarian hormones on the consumption of psychoactive substances in rodents, adhering to the PRISMA 2009 protocol. Our findings underscore the significant role of ovarian hormones, particularly oestrogen, in augmenting drug consumption among female rodents. Notably, with heroin, it was observed that progesterone, rather than oestrogen, facilitated increased consumption in female rodents. The susceptibility to addiction influenced by oestrogen is accentuated across distinct phases, and the molecular mechanisms form a complex interplay that significantly influences addictive behaviours. By bringing together these findings, we aim to establish a strong foundation for future studies. This work may guide clinical investigations in developing more effective prevention or treatment strategies that address the unique vulnerabilities of females to substance use disorders.