Marked decrease of plasma neuroactive steroids during alcohol withdrawal

The neuroactive steroids allopregnanolone (ALLO) and allotetrahydrodeoxycorticosterone (THDOC) are the most potent endogenous positive modulators of γ-aminobutyric acid (GABA) on GABA(A) receptors, a receptor system presumably responsible for some behavioral responses to alcohol withdrawal. In a group of nine alcoholic subjects, the levels of plasma ALLO and THDOC were markedly lower than those of control subjects during the early withdrawal phase (day 4 and 5), when anxiety and depression scores were higher. In contrast ALLO and THDOC plasma levels did not differ from those of control subjects during the late withdrawal phase when anxiety and depression scores were low. These results suggest that the decrease of neuroactive steroid biosynthesis may contribute to the withdrawal symptoms.