Fear-motivated Behavior Induced by Prior Shock Experience is Mediated by Corticotropin-releasing Hormone Systems

In earlier studies, we established that in rats, antagonism of corticotropin-releasing hormone (CRH) receptors reduced the occurrence of fear-motivated behavior displayed immediately after administration of electric foot shock. Because exposure to stress is reported to have long-term behavioral and physiological effects, we examined whether central administration of the synthetic CRH receptor antagonist, alpha-helical CRH(9-41), would also alter fear-motivated behavioral and hormonal responses occurring 24 h after exposure to electric foot shock. Adult male rats were placed in a shock box and administered three, 1.0 mA foot shocks. Twenty-four hours later, rats received an intracerebroventricular infusion of 20 micrograms of alpha-helical CRH(9-41) or vehicle 20 min before re-exposure to the shock box. Antagonism of CRH receptors produced a significant reduction in fear-motivated freezing. However, stress-induced analgesia and plasma adrenocorticotropin concentrations did not differ significantly from vehicle-treated animals. In order to assess whether the reduction in freezing was due to intrinsic actions of the CRH receptor antagonist, non-shocked rats received central infusions of alpha-helical CRH(9-41) prior to re-exposure to the test box. Under these conditions, behavior exhibited by antagonist- and vehicle-treated rats did not differ significantly. Results suggest that the reduction in fear-motivated behavior is mediated by antagonism of endogenous CRH receptors and occurs independently of analgesic and hormonal reactions induced by prior exposure to stress.