Central CRF Receptor Antagonist α-Helical CRF9-41 Blocks Reinstatement of Extinguished Fear: The Role of the Bed Nucleus of the Stria Terminalis

The present experiments assessed the necessity of central CRF in reinstatement of extinguished fear. Using the fear-potentiated startle procedure, rats were given light-shock pairings (fear conditioning) followed by light-alone extinction training. Rats were then given unsignaled shocks to reinstate fear to the light conditioned stimulus (CS). Intracerebroventricular administration of the CRF antagonist a-Helical CRF9-41 prior to reinstatement training dose-dependently prevented reinstatement. Further, a-Helical CRF9-41 administration prior to reinstatement training or the test for reinstatement of fear to the extinguished CS prevented reinstatement at both treatment times, suggesting that CRF activity is critical for this type of return of fear to an extinguished CS. The abolition of reinstatement by drug administration was not due to state-dependent learning, as rats treated with the drug prior to both reinstatement training or testing also failed to show reinstatement of fear. Local administration of a-Helical CRF9-41 in the bed nucleus of the stria terminalis suggested that this area is a site at which central CRF is involved in this form of relapse.