ABSTRACT
These receptors are the site of action of various pharmacologically and clinically important drugs, such as benzodiazepines, barbiturates, general anesthetics and convulsants3,6. Inaddition, a large body of experimental evidence has been provided in the past decade indicating that steroid hormones synthesized in the brain and periphery are among the most selective, potent and efficacious allosteric modulators of GABAA receptors identified to date. The term neurosteroids refers to steroid derivatives that are synthesized de novo from cholesterol in the central nervous system7-11. The action of some of these neurosteroids, such as 3α, 5α-tetrahydroprogesterone (3α, 5α-TH PROG or allopregnanolone) and 3α, 5α-tetrahydro-deoxycorticosterone (3α, 5α-TH DOC) at GABAA receptors results in a rapid onset and offset strong potentiation of GABA-evoked inhibitory postsynaptic Cl− currents12-15, withpotency and efficacy similar to or greater than that of benzodiazepines and barbiturates13,14,16. Neurosteroids are thus considered the endogenous modulators of GABAA receptor-mediated neurotransmission. Modulation of synaptic activity through the interaction of neurosteroids with membrane-bound ionotropic neurotransmitter receptors11-15,17,18 thus represents a mechanism of action of steroid hormones additional to the classic genomic action of these compounds19.
