The role of progestins in the behavioral effects of cocaine and other drugs of abuse: Human and animal research

Abstract

This review summarizes findings from human and animal research investigating the influence of progesterone and its metabolites allopreganolone and pregnanolone (progestins) on the effects of cocaine and other drugs of abuse. Since a majority of these studies have used cocaine, this will be the primary focus; however, the influence of progestins on other drugs of abuse will also be discussed. Collectively, findings from these studies support a role for progestins in: 1) attenuating the subjective and physiological effects of cocaine in humans, 2) blocking the reinforcing and other behavioral effects of cocaine in animal models of drug abuse, and 3) influencing behavioral responses to other drugs of abuse such as alcohol and nicotine in animals. Administration of several drugs of abuse in both human and nonhuman animals significantly increased progestin levels, and this is explained in terms of progestins acting as homeostatic regulators that decrease and normalize heightened stress and reward responses which lead to increased drug craving and relapse. The findings discussed here highlight the complexity of progestin-drug interactions, and they suggest a possible use for these agents in understanding the etiology and developing treatments for drug abuse.

Progesterone and Postpartum Smoking Relapse: A Pilot Double-Blind Placebo-Controlled Randomized Trial

“…Given the preclinical 14,15 and clinical literature [16][17][18][19][20] which supports the role of progesterone as attenuating addictive behavior and given the erratic change of gonadal hormones in the postpartum period we hypothesized that administering exogenous progesterone to postpartum women could potentially prevent postpartum relapse. Our observations indicate that there was moderate to high compliance and high acceptability of administering exogenous progesterone to women in the immediate postpartum period.…”

“…This is strongly supported by preclinical work 14,15 but clinical studies are mixed. [16][17][18][19][20] In pregnancy, progesterone increases by more than 10 fold and certain estrogen levels increase by up to 1000 fold, then within the first few hours postpartum levels drop to near pre pregnancy levels.…”

Nicotine Withdrawal Increases Stress-Associated Genes in the Nucleus Accumbens of Female Rats in a Hormone-Dependent Manner

“…Future studies might also examine the role of other ovarian hormones, such as progesterone that have been posited to modulate tobacco use in females. 29,30 In the present study, female rats received OVX procedures before puberty. Future studies might examine the activational effects of ovarian hormones on stress produced by nicotine withdrawal in females that receive OVX procedures during adulthood.…”

Estradiol as a Mechanism for Sex Differences in the Development of an Addicted Phenotype following Extended Access Cocaine Self-Administration

“…This model does not attempt to mimic normal cyclicity observed in intact females, and it does not account for the role of other ovarian hormones, such as progesterone, which appears to have a key role in modulating vulnerability to cocaine addiction in females (Anker and Carroll, 2010). Despite its limitations, however, this model provides a powerful tool for assessing estradiol's specific contribution to cocaine addiction vulnerability.…”