Effects of corticotropin-releasing factor on prepulse inhibition of the acoustic startle response in two rat strains.
BACKGROUND
Prepulse inhibition (PPI) of the acoustic startle response is altered by manipulations that affect brain monoamine neurotransmission. Corticotropin-releasing factor (CRF), a neurotransmitter that is released during stress, and CRF receptors are expressed in areas of the brain which contribute to PPI, and central administration of CRF changes extracellular concentrations of the monoamines. Therefore, CRF is in a position to alter PPI, either by causing the release of other neurotransmitters, or by direct effects at CRF receptors.


OBJECTIVE
The present experiments were conducted to test the hypothesis that intracerebroventricular (ICV) administration of CRF would decrease PPI in rats. Additionally, these experiments were used to examine whether CRF results in differential changes in PPI in rat strains that show high and low basal PPI, and whether CRF-induced grooming behavior and increased startle amplitude are also strain-dependent.


METHODS
Male Wistar-Kyoto (WKY) rats inbred in our colony in La Jolla, WKY rats obtained from Charles River, and Brown Norway (BN) rats from Harlan, Sprague-Dawley were tested for grooming behavior, PPI and startle amplitude following ICV infusion of either CRF (1.0-3.0 microg) or saline.


RESULTS
CRF significantly decreased PPI in both BN rats, which show relatively little PPI in the basal condition and, in WKY rats. The amplitude of the acoustic startle response was increased in WKY rats only and, only by the 3.0 microg dose of CRF. CRF increased grooming behavior in the La Jolla colony WKY and BN rats. However, within the time frame during which the rats were being observed, CRF failed to significantly increase grooming in Charles River WKY rats.


CONCLUSIONS
CRF diminished PPI of the acoustic startle response in rats that show high (WKY) and low (BN) basal PPI. This effect does not appear to be dependant on CRF-induced changes in startle amplitude. The results suggest the possibility that stress-induced exacerbation of symptoms in schizophrenia, which is characterized by deficient PPI, may be CRF-dependent.
Conti
Lisa H
LH
Department of Pharmacology, 0636, University of California, San Diego, 9500 Gilman Drive, La Jolla 92093, USA. Lconti@ucsd.edu
Murry
Jennifer D
JD
Ruiz
Mark A
MA
Printz
Morton P
MP
D000161:Acoustic Stimulation; D000704:Analysis of Variance; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006120:Grooming / Q000187:drug effects; D007260:Infusion Pumps; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D013216:Reflex, Startle / Q000187:drug effects*; D013045:Species Specificity
D003346:Corticotropin-Releasing Hormone