Sigma 1 Receptor-Related Neuroactive Steroids Modulate Cocaine-Induced Reward

The study investigated the role of sigma1 receptor-related neuroactive steroids in modulating cocaine-induced reward using the conditioned place preference (CPP) procedure in C57BL/6 mice. It was found that neuroactive steroids like DHEA and pregnenolone, which act as sigma1 receptor agonists, enhanced cocaine-induced CPP when administered during conditioning. Conversely, progesterone, a sigma1 receptor antagonist, and finasteride, a 5alpha-reductase inhibitor, blocked the acquisition of cocaine-induced CPP. The sigma1 antagonist BD1047 also blocked the potentiating effects of DHEA and pregnenolone on cocaine-induced CPP. These findings suggested that neuroactive steroids influence cocaine-induced reward through interactions with the sigma1 receptor, highlighting their potential role in individual vulnerability to drug addiction. The study involved groups of mice ranging from 8 to 26 per experiment.