The effect of corticotropin-releasing factor on prepulse inhibition is independent of serotonin in Brown Norway and Wistar-Kyoto rats.

Prepulse inhibition (PPI), a form of sensorimotor gating, is reduced in a number of psychiatric disorders. Two experiments were conducted to determine whether corticotropin-releasing factor (CRF), which decreases PPI, does so via effects on serotonin (5-HT). Wistar-Kyoto (WKY) and Brown Norway (BN) rats were used in both experiments in order to examine whether strain-dependent differences would be apparent in response to manipulations of the CRF and 5-HT systems. In the first experiment, WKY and BN rats received a subcutaneous injection of the 5-HT(2A/C) receptor antagonist, ketanserin (2.0 mg/kg). Ten minutes later, rats received an intracerebroventricular (ICV) infusion of either 6.0 microl saline or CRF (0.3 microg or 3.0 microg). CRF decreased PPI despite blockade of 5-HT(2A/C) receptors with ketanserin. In the second experiment, WKY and BN rats received an intraperitoneal injection of the 5-HT synthesis inhibitor, p-chlorophenylalanine (PCPA, 150 mg/kg), 48 and 24 h prior to testing. On testing day, rats received an ICV infusion of either 6.0 microl saline or CRF (0.3 microg or 3.0 microg). CRF decreased PPI despite 5-HT depletion. These findings suggest that CRF does not decrease PPI via effects on 5-HT, since neither blockade of 5-HT(2A/C) receptors nor 5-HT depletion attenuated this decrease.