Characterization of the effects of corticotropin-releasing factor on prepulse inhibition of the acoustic startle response in Brown Norway and Wistar-Kyoto rats

Abstract

Sensori-motor gating, as assessed by prepulse inhibition of the startle response is diminished in patients with schizophrenia. We have previously shown that inbred Brown Norway (BN) rats display significantly less prepulse inhibition of the acoustic startle response than inbred Wistar-Kyoto (WKY) rats, and that prepulse inhibition is decreased by central administration of the neuropeptide, corticotropin-releasing factor (CRF) in both strains. The present study was conducted to establish whether peripheral administration of CRF alters prepulse inhibition, whether a low, threshold dose for decreasing prepulse inhibition is the same in the two rat strains, and whether central administration of a CRF receptor antagonist enhances prepulse inhibition in the BN strain. CRF-induced behavioral activation was also examined to determine whether the two rat strains are differentially sensitive to a behavioral effect of CRF that does not involve the startle response. In each experiment, BN rats showed significantly less prepulse inhibition than WKY rats. Subcutaneous administration of CRF had no affect on startle amplitude or prepulse inhibition of the startle response in either rat strain. In BN, but not in WKY rats, low-dose CRF (0.3 microg) decreased prepulse inhibition. However, doses of CRF that did not alter prepulse inhibition in the WKY strain, did result in behavioral activation. No dose of CRF tested affected baseline startle amplitude. Central administration of the CRF receptor antagonist, astressin had no effect on prepulse inhibition or startle amplitude in either rat strain. Central administration of the CRF receptor antagonist, D-Phe CRF (12-41) had no effect on prepulse inhibition in WKY rats, resulted in a only a small, non-significant increase in prepulse inhibition in BN rats, while it decreased startle amplitude. The results suggest that CRF reduces prepulse inhibition of the acoustic startle response independently of effects on the pituitary-adrenal axis, and that endogenous CRF has at most, a minor role in the low prepulse inhibition found in BN rats.