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

    May 2003 in “ Journal of Neuroscience ”
    Pascal Romieu, Rémi Martin‐Fardon, Wayne D. Bowen, Tangui Maurice
    TLDR Neuroactive steroids affect cocaine's rewarding effects through the ς<sub>1</sub> receptor.
    The study demonstrated that the ς<sub>1</sub> receptor was crucial in the rewarding effects of cocaine, as observed in C57BL/6 mice using the conditioned place preference (CPP) procedure. Neuroactive steroids like DHEA and pregnenolone acted as agonists at the ς<sub>1</sub> receptor, enhancing cocaine-induced CPP, while progesterone and finasteride, a 5α-reductase inhibitor, blocked it. The ς<sub>1</sub> 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 ς<sub>1</sub> receptor, suggesting that neuroendocrine control of cocaine addiction involved more than just glucocorticoids and highlighting the potential role of neuroactive steroids in individual vulnerability to drug addiction.
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