It has been recognised over the past 20 years that that certain steroids synthesised de novo in the brain (hence named neurosteroids) can produce immediate changes (within seconds) in neuronal excitability, on a time scale that precludes a genomic locus of action. Identified molecular targets underlying modulation of brain excitability, include both the inhibitory GABA-A and the excitatory NMDA receptors. Of particular interest is the interaction of certain neurosteroids with the GABA-A receptor, the major inhibitory receptor in the mammalian brain. During the last few years compelling evidence has been presented demonstrating that neurosteroids act locally to selectively "fine tune" neuronal inhibition. A range of molecular mechanisms including the subunit composition of the receptor(s), phosphorylation mechanisms and local metabolism govern the non-genomic modulation of synaptic and extra-synaptic GABA-A receptors by a range of endogenous and synthetic neuroactive steroids and underpin their region and neurone-selectivity (Belelli & Lambert 2005; Herd et al. 2007). Here, we will review the current understanding of the relative impact each of these mechanisms has on neurosteroid action within specific neuronal circuits and the relevance of these effects to the role of neurosteroids in health and disease.

References: 

Belelli, D. & Lambert, J.J. 2005. Nature Rev. Neurosci. 6(7), 565–75. Herd, M.B., Belelli, D. & Lambert, J.J. 2007. Pharmacol. Ther. 116(1), 20–34.