Antagonism of endogenous CRH systems attenuates stress-induced freezing behavior in rats.

Three experiments were conducted to test the hypothesis that brain corticotropin-releasing hormone (CRH) systems mediate stress-induced freezing behavior, an index of a rat's level of fear. We administered i.c.v. 0-50 micrograms of alpha-helical CRH9-41 (a specific CRH antagonist) before foot shock and showed that this peptide had little effect on baseline preshock behavior but significantly attenuated the occurrence of shock-induced freezing. We concluded that this attenuation of freezing behavior was not related to the effects of alpha-helical CRH9-41 on the animals' sensitivity to pain, because no significant effects on latency to respond on a hot-plate test of pain sensitivity were found. We also showed that alpha-helical CRH9-41 has a relatively rapid time course of action when administered i.c.v., since it blocked shock-induced freezing when given 20 min but not 40 min before foot shock. Our findings suggest that endogenous CRH systems mediate stress-induced, fear-related behavior through mechanisms other than alteration of nociceptive systems.