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.
Sutherland
Jane E
JE
Department of Psychiatry and Neuroscience Program, University of Connecticut Health Center, Farmington, CT 06030, USA.
Page
Michelle E
ME
Conti
Lisa H
LH
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D010134:Fenclonine / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011921:Rats, Inbred WKY; D013216:Reflex, Startle / Q000187:drug effects*; D012701:Serotonin / Q000502:physiology*; D013045:Species Specificity
D012701:Serotonin; D003346:Corticotropin-Releasing Hormone; D007650:Ketanserin; D010134:Fenclonine