Progesterone attenuates corticotropin-releasing factor-enhanced but not fear-potentiated startle via the activity of its neuroactive metabolite, allopregnanolone

J Neurosci. 2004 Nov 10;24(45):10280-7. doi: 10.1523/JNEUROSCI.1386-04.2004.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Anxiety
  • Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Estradiol / administration & dosage
  • Estradiol / pharmacology
  • Fear / drug effects*
  • Female
  • Hormone Replacement Therapy
  • Lactation / physiology
  • Medroxyprogesterone / pharmacology
  • Ovariectomy
  • Pregnancy
  • Pregnanolone / physiology*
  • Progesterone / administration & dosage
  • Progesterone / blood
  • Progesterone / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reflex, Startle / drug effects*
  • Reflex, Startle / physiology
  • Septal Nuclei / drug effects*
  • Septal Nuclei / physiology

Substances

  • Progesterone
  • Estradiol
  • Corticotropin-Releasing Hormone
  • Pregnanolone
  • Medroxyprogesterone