Role of GABA-Active Neurosteroids in the Efficacy of Metyrapone Against Cocaine Addiction

The study explored the role of GABA-active neurosteroids in the effectiveness of metyrapone, a glucocorticoid biosynthesis inhibitor, against cocaine addiction. Metyrapone was shown to reduce cocaine-related behaviors in rodents, and its combination with oxazepam decreased drug-seeking behaviors in both animals and humans. The research suggested that metyrapone's effects were not solely due to glucocorticoid suppression, as it did not significantly alter plasma corticosterone levels. Instead, the study highlighted the potential involvement of neurosteroids, such as allopregnanolone and THDOC, which modulate GABAA receptors and may contribute to metyrapone's efficacy. The findings indicated that neurosteroids could be a critical mechanism in reducing cocaine self-administration, as evidenced by experiments with male Wistar rats.