This chapter has summarized some key advances in the chemistry and pharmacology of natural and synthetic steroids (neuroactive steroids) that modulate the action of GABA, a major inhibitory neurotransmitter in the brain. Attention has also been focused on the potential role of GABAergic neurosteroids in alcohol dependence and withdrawal, as well as in affective disorders. These are two areas where a growing body of evidence

Fig. 3. Metabolic pathway for the formation of allopregnanolone (3a,5a-TH PROG) and pregnanolone (3a,5p-TH PROG).

suggests that these steroids may play a role in the behavioral and neuroendocrine consequences of stress-induced disorders. The now well-characterized interaction of neuro-active steroids with GABAa receptors will continue to prompt further efforts to delineate the mechanism of action of steroids on neuronal membranes, with emphasis on the rapid alteration of neuronal excitability.

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