NEUROSTEROID MODULATION OF ARTERIAL BAROREFLEX-SENSITIVE NEURONS IN RAT ROSTRAL VENTROLATERAL MEDULLA

The major metabolite of progesterone, 3 alpha-OH-dihydroprogesterone ( 3 alpha-OH-DHP), is the most potent endogenous positive modulator of c entral nervous system GABA(A) receptors. Acute intravenous administrat ion of 3 alpha-OH-DHP to virgin female rats potentiates arterial baror eflex sympathoinhibitory responses. The current experiments tested the possibility that circulating 3 alpha-OH-DHP potentiates central GABAe rgic influences in the rostral ventrolateral medulla (RVLM). The unit activity of spontaneously active, spinally projecting, and arterial pr essure-sensitive neurons was recorded in the RVLM of urethan-anestheti zed rats. Arterial pressure sensitivity of RVLM neurons was tested bef ore (control) and 10 min after bolus injection (44 mu l iv) of 3 alpha -OH-DHP (1.12 mu g/kg, n = 19) or vehicle (40% beta-cyclodextrin, n = 8). Both threshold pressure and saturation pressure for inhibition of RVLM neurons were decreased after acute administration of a physiologi cal dose of 3 alpha-OH-DHP (1.12 mu g/kg iv), which produces plasma co ncentrations similar to those seen during pregnancy (20-30 ng/ml), sug gesting potentiated responsiveness to endogenously released GABA. Foll owing suppression by 3 alpha-OH-DHP, high doses of the inactive stereo isomer 3 beta-OH-DHP (112-224 mu g/kg iv; n = 8) restored unit activit y, presumably by displacing 3 alpha-OH-DHP from the neurosteroid bindi ng site on GABAA receptors.