During the past 15 years it became evident that the brain is capable of the de novo synthesis of steroids called "neurosteroids," which have been recognized as important regulators of neuronal activities (1,2). The definition of "neurosteroids" encompasses the steroids synthesized in nervous tissues as well as some adrenal and gonadal steroids that directly affect neurotransmission. Although estrogens, androgens and glucocorticoids are also neuroactive, they are generally not considered as neurosteroids, because their genomic actions generalize to their activities in other tissues. The synthesis of neurosteroids is discussed in other chapters of this monograph and will not be addressed here. This chapter describes biochemical, physiological, and behavioral aspects of the GABAa receptor antagonistic actions of neurosteroids, primarily pregnenolone sulfate (PREGS) and dehydroepiandrosterone sulfate (DHEAS), and discusses their psycho-physio-pathological significance (for comprehensive review, see ref. 2). PREGS and DHEAS are present in significant amounts in brains of different species, ranging from rodents to primates, including humans (3-6).

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