Regulation of cocaine-related behaviours by estrogen and progesterone

Women are more sensitive to cocaine craving elicited by stimuli associated with relapse. Ovarian hormones modulate cocaine craving and may therefore function as risk factors or therapeutic agents for the development and treatment of cocaine use disorder, respectively. We review herein the neuropharmacological effects of the steroid hormones 17 ss-estradiol, progesterone, and allopregnanolone, a progesterone metabolite, in relation to their effects on cocaine-induced locomotion, behavioural sensitization, conditioned place preference, and reinstatement of cocaine seeking. In general, the literature suggests that female rats are more sensitive to these cocaine-induced behaviours than males and that 17 ss-estradiol facilitates the expression of these sex differences. Alternatively, in females, exogenous progesterone attenuates cocaine conditioned place preference, reinstatement, and possibly behavioural sensitization, either on its own or after conversion to allopregnanolone. These opposing effects of 17 ss-estradiol and progesterone/allopregnanolone involve endocannabinoid, gamma-aminobutyric acid, dopamine, and glutamate transmission in the medial prefrontal cortex and striatum. We conclude that 17 ss estradiol may be a risk factor for various components of cocaine use disorder in women, whereas progesterone and allopregnanolone may be potential treatment options.

Automated summary

Women are more sensitive to cocaine craving triggered by relapse-related stimuli, and ovarian hormones modulate cocaine craving, potentially serving as risk factors or therapeutic agents for cocaine use disorder. The neuropharmacological effects of steroid hormones 17β-estradiol, progesterone, and allopregnanolone on cocaine-induced behaviors differ between female and male rats, with estradiol potentially being a risk factor and progesterone/allopregnanolone serving as potential treatment options for various components of cocaine use disorder in women.