Concluding Remarks

The selectivity of the neurosteroids for the GABAA receptor, their impressive potency, together with the demonstration that the CNS can synthesize such agents, strongly suggests this steroid-neurotransmitter interaction may subserve an important physiological or pathophysiological role. However, to clarify such an endogenous role, there is a urgent requirement for a potent, and selective, neurosteroid antagonist, analogous to the benzodiazepine receptor antagonist, flumazenil (6). Furthermore, the development of a selective radioligand, used in conjunction with appropriate genetically modified recombinant GABAA receptors, may permit the identification of the neurosteroid binding domain(s) on the receptor protein. Whether or not the steroids play a physiological role, they have clear behavioral effects and these may in the future be exploited for therapeutic benefit.

Finally, some of the GABA-active steroids described here are metabolites of hormones that do exert genomic effects in the CNS. Hence, steroids may influence brain activity, and therefore behavior, by a complex interaction of transcriptional and nongenomic actions.

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