RT Journal Article
SR Electronic
T1 Progesterone Attenuates Corticotropin-Releasing Factor-Enhanced But Not Fear-Potentiated Startle via the Activity of Its Neuroactive Metabolite, Allopregnanolone
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 10280
OP 10287
DO 10.1523/JNEUROSCI.1386-04.2004
VO 24
IS 45
A1 Toufexis, Donna J.
A1 Davis, Carrie
A1 Hammond, Alexis
A1 Davis, Michael
YR 2004
UL http://www.jneurosci.org/content/24/45/10280.abstract
AB 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 μg 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.