Neuroactive Steroids: Functions, Mechanisms of Action, and Physiological Relevance

The study explored the effects of progesterone (PROG) and its metabolite allopregnanolone (AP) on GABA-A receptor subunits in neurons, noting that chronic exposure led to decreased receptor subunit abundance and altered efficacy of modulators. Similar changes were observed with ethanol (ETH) exposure. Withdrawal from PROG and ETH increased a4 subunit mRNA and restored receptor sensitivity. The research suggested a synergistic action between ETH and AP in modulating dopamine neurons, which are involved in addiction. Injection of PROG increased AP levels and enhanced ETH's effects on dopamine output, effects that were blocked by finasteride. This indicated that AP might play a crucial role in ETH's impact on neurons related to alcohol abuse vulnerability.