NEUROSTEROID MODULATION OF [H-3] FLUNITRAZEPAM BINDING IN THE MEDULLA- AN AUTORADIOGRAPHIC STUDY

Neurosteroids bind to unique sites on the GABA(A) receptor complex and modulate receptor function. The effects of neurosteroids on GABA(A) r eceptors have been well characterized in forebrain regions. However, l ittle is known about their effects on GABA(A) receptors in the medulla , especially those areas involved in autonomic reflex pathways. Stimul ation of [H-3]flunitrazepam binding to the GABA(A) receptor by two pro gesterone metabolites, 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha -OH-DHP) and 3 beta-hydroxy-5 alpha-pregnan-20-one (3 beta-OH-DHP), wa s studied using autoradiographic methods in the medulla and cerebellum of female rats at estrus. [H-3]Flunitrazepam binding was enhanced by 3 alpha-OH-DHP in every nucleus examined in the medulla and cerebellum This effect was stereoselective since 3 beta-OH-DHP had no effect on binding in any region. No differences were observed in the degree of s timulation of [H-3]flunitrazepam binding by 3 alpha-OH-DHP among medul lary brain regions. However, in the cerebellum, the stimulation of bin ding was significantly greater in the granular layer than in the molec ular layer. Stimulation of [H-3]flunitrazepam binding by 3 alpha-OH-DH P in nuclei involved in the baroreflex pathways supports previous stud ies which report that neurosteroids modulate autonomic regulation of b lood pressure. These actions may also underlie alterations in autonomi c function during pregnancy. (C) 1997 Elsevier Science B.V.