The endogenous 3a-hydroxy ring A-reduced steroids allopregnanolone and pregna-nolone are among the most active ligands of gamma amino butric acid A (GABAa) receptors, with affinities equal to or greater than those of other known ligands such as barbiturates, and even benzodiazepines (1,2). It is, therefore, not surprising that numerous 3a-hydroxy steroids have anxiolytic, hypnotic, anticonvulsant, and anesthetic effects when administered to laboratory animals (2). These pharmacological actions, together with their low intrinsic toxicity and lack of hormonal activity, have led an expanding number of laboratories to investigate their physiological and pharmacological properties in both laboratory animals and humans. Efforts are also underway to develop novel synthetic anxiolytic, hypnotic, and anticonvulsant steroids as therapeutic agents. In this chapter, we discuss a few selected areas related to the pharmacology, physiology, and chemistry of GABAergic neuroactive steroids, including their potential roles in alcohol dependence and withdrawal, as well as in affective disorders.

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