Neurosteroids: endogenous regulators of the GABAA receptor

Abstract
GABAA (γ-aminobutyric acid type A) receptors mediate most of the 'fast' synaptic inhibition in the mammalian brain and are targeted by many clinically important drugs. Certain naturally occurring pregnane steroids can potently and specifically enhance GABAA receptor function in a nongenomic (direct) manner, and consequently have anxiolytic, analgesic, anticonvulsant, sedative, hypnotic and anaesthetic properties. These steroids not only act as remote endocrine messengers, but also can be synthesized in the brain, where they modify neuronal activity locally by modulating GABAA receptor function. Such 'neurosteroids' can influence mood and behaviour in various physiological and pathophysiological situations, and might contribute to the behavioural effects of psychoactive drugs.