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Department of Physiology, The Ohio State University, Columbus, Ohio 43210-1218
The major metabolite of progesterone,
3
-OH-dihydroprogesterone (3-OH-DHP), is the most potent
endogenous positive modulator of central nervous system
GABAA receptors. Acute intravenous
administration of 3-OH-DHP to virgin female rats potentiates
arterial baroreflex sympathoinhibitory responses. The current
experiments tested the possibility that circulating 3-OH-DHP
potentiates central GABAergic influences in the rostral
ventrolateral medulla (RVLM). The unit activity of spontaneously
active, spinally projecting, and arterial pressure-sensitive neurons
was recorded in the RVLM of urethan-anesthetized rats. Arterial
pressure sensitivity of RVLM neurons was tested before (control) and 10 min after bolus injection (44 µl iv) of 3-OH-DHP (1.12 µg/kg,
n = 19) or vehicle (40%
-cyclodextrin, n = 8). Both
threshold pressure and saturation pressure for inhibition of RVLM
neurons were decreased after acute administration of a physiological
dose of 3-OH-DHP (1.12 µg/kg iv), which produces plasma
concentrations similar to those seen during pregnancy (20-30 ng/ml), suggesting potentiated responsiveness to endogenously released
GABA. Following suppression by 3-OH-DHP, high doses of the inactive
stereoisomer 3-OH-DHP (112-224 µg/kg iv;
n = 8) restored unit activity,
presumably by displacing 3-OH-DHP from the neurosteroid binding site
on GABAA receptors.
-aminobutyric acid; baroreflex; progesterone
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