Restraint stress-induced reduction in prepulse inhibition in Brown Norway rats: Role of the CRF2 receptor

Stress plays a role in many psychiatric disorders that are characterized by deficits in prepulse inhibition (PPI), a form of sensorimotor gating. Corticotropin-releasing factor (CRF) is one of the most important neurotransmitters involved in behavioral components of the stress response. Central infusion of CRF reduces PPI in both rats and mice. In mice, it has been shown that CRF1 receptor activation mediates the effect of exogenous CRF on PPI. However, the roles of the two CRF receptors in a stress-induced reduction in PPI are not known. We sought to determine whether CRF1 and/or CRF2 receptor blockade attenuates a stress-induced reduction of PPI in rats. In separate experiments, we assessed PPI in Brown Norway rats after exposure to 5 days of 2-h restraint, and after pretreatment with the CRF1 receptor antagonist, CP-154,526 (20.0 mg/kg), or the CRF2 receptor antagonist, antisauvagine-30 (10.0 μg). Repeated, but not acute, restraint decreased PPI and attenuated the increase in PPI caused by repeated PPI testing. Blockade of the CRF1 receptor did not attenuate the effect of repeated restraint on PPI or grooming behavior. While CRF2 receptor blockade did attenuate the effect of repeated restraint on PPI, repeated ICV infusion of the selective CRF2 receptor agonist urocortin III, did not affect PPI. These findings demonstrate the effect of stress on sensorimotor gating and suggest that the CRF2 receptor mediates this effect in rats.