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 central nervous system GABAA receptors. Acute intravenous administration of 3 alpha-OH-DHP to virgin female rats potentiates arterial baroreflex sympathoinhibitory responses. The current experiments tested the possibility that circulating 3 alpha-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 microliters i.v.) of 3 alpha-OH-DHP (1.12 micrograms/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 physiological dose of 3 alpha-OH-DHP (1.12 micrograms/kg i.v.), 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 alpha-OH-DHP, high doses of the inactive stereoisomer 3 beta-OH-DHP (112-224 micrograms/kg i.v.; n = 8) restored unit activity, presumably by displacing 3 alpha-OH-DHP from the neurosteroid binding site on GABAA receptors.
Laiprasert
J D
JD
Department of Physiology, Ohio State University, Columbus 43210-1218, USA.
Rogers
R C
RC
Heesch
C M
CM
D000818:Animals; D001158:Arteries / Q000294:innervation*; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D004056:Differential Threshold; D005260:Female; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009994:Osmolar Concentration; D011280:Pregnanolone / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D005680:gamma-Aminobutyric Acid; D011280:Pregnanolone