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

The study demonstrated that the sigma1 receptor was crucial in the rewarding effects of cocaine, as observed in mice using the conditioned place preference (CPP) procedure. Neuroactive steroids like DHEA and pregnenolone acted as agonists at the sigma1 receptor, enhancing cocaine-induced CPP, while progesterone acted as an antagonist, blocking this effect. The sigma1 antagonist also blocked cocaine-induced CPP and its enhancement by DHEA or pregnenolone. These findings indicated that neuroactive steroids influenced cocaine-induced reward through the sigma1 receptor, suggesting that neuroendocrine control of cocaine addiction involved more than just glucocorticoids, highlighting the potential role of neuroactive steroids in individual vulnerability to drug addiction.