Progesterone attenuates corticotropin-releasing factor-enhanced but not fear-potentiated startle via the activity of its neuroactive metabolite, allopregnanolone.
Intact female rats and ovariectomized (OVX) rats with different ovarian steroid replacement regimens were tested for changes in corticotropin-releasing factor (CRF)-enhanced startle (increased acoustic startle amplitude after intracerebroventricular infusion of 1 mug of CRF). OVX rats injected with estradiol (E) followed by progesterone (P) showed a blunted CRF-enhanced startle effect compared with OVX and E-injected rats. CRF-enhanced startle also was reduced significantly in lactating females (high endogenous P levels) compared with cycling rats (low to moderate P levels), as well as in non-E-primed rats when P was administered acutely (4 hr before testing) or chronically (7 d P replacement). The ability of P to attenuate CRF-enhanced startle was probably mediated by its metabolite allopregnanolone [tetrahydroprogesterone (THP)], because THP itself had a similar effect, and chronic administration of medroxyprogesterone, which is not metabolized to THP, did not blunt CRF-enhanced startle but instead slightly increased it. These data suggest that P blunts CRF-enhanced startle through a mechanism involving its neuroactive metabolite THP, although a role for the P receptor cannot be completely ruled out. Finally, neither chronic P replacement nor acute THP affected fear-potentiated startle, suggesting that P metabolites have an effect on the bed nucleus of the stria terminalis and anxiety rather than on the amygdala and stimulus-specific fear.
Toufexis
Donna J
DJ
Department of Psychiatry and Behavioral Sciences and The Center for Behavioral Neuroscience, Emory University School of Medicine, Atlanta, Georgia 30322, USA. dtoufe@yahoo.com
Davis
Carrie
C
Hammond
Alexis
A
Davis
Michael
M
D000161:Acoustic Stimulation; D000818:Animals; D001007:Anxiety; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D005239:Fear / Q000187:drug effects*; D005260:Female; D020249:Hormone Replacement Therapy; D007774:Lactation / Q000502:physiology; D008525:Medroxyprogesterone / Q000494:pharmacology; D010052:Ovariectomy; D011247:Pregnancy; D011280:Pregnanolone / Q000502:physiology*; D011374:Progesterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D012686:Septal Nuclei / Q000187:drug effects* / Q000502:physiology
D011374:Progesterone; D004958:Estradiol; D003346:Corticotropin-Releasing Hormone; D011280:Pregnanolone; D008525:Medroxyprogesterone