A stress-induced anxious state in male rats: Corticotropin-releasing hormone induces persistent changes in associative learning and startle reactivity

Background Exposure to intense inescapable stressors induces a persistent anxious state in rats. The anxious state is evident as increased sensory reactivity and enhanced associative learning. Methods We examine whether similar neurobehavioral changes are observed after intracerebroventricular (ICV) administration of corticotropin releasing hormone (CRH). Two behaviors were observed: acoustic startle responses (ASRs) and acquisition of the classically conditioned eyeblink response. Male Sprague-Dawley rats were administered ICV CRH either in a single dose (1.0 μg/rat) or in three doses each separated by 30 min. Results Exaggerated ASRs were evident 2 hours after either CRH treatment; however, only the rats given three injections exhibited a persistently exaggerated ASR apparent 24 hours after CRH treatment. Rats administered three injections of CRH also exhibited faster acquisition of the eyeblink conditioned response beginning 24 hours after treatment. Yet, we did not find evidence for a persistent activation of the HPA-axis response; three CRH injections did not lead to elevated basal plasma corticosterone levels the following morning. Conclusions Repeated treatment with CRH over a 1.5-hour period models some of the behavioral changes observed after exposure to intense inescapable stressors.