AUTONOMIC AND BEHAVIORAL-EFFECTS OF CENTRALLY ADMINISTERED CORTICOTROPIN-RELEASING FACTOR IN RATS

Changes in heart rate, core temperature, and gross locomotor activity were recorded simultaneously by a wireless telemetry system for periods up to 60 min after intracerebroventricular (icv) administration of synthetic human CRF-(1-41) (CRF) or artificial cerebrospinal fluid in rats in their home cages. The telemetry system provides a highly sensitive method to monitor autonomic nervous system (ANS) activity without imposing restraint on the animal. CRF was administered at lower doses than hitherto used to study central effects on the ANS (0.03, 0.1, 0.3, and 1-mu-g). Starting 10 min after icv injections, behavioral responses to CRF, i.e. grooming, locomotion, and digging, were determined by a time sampling method. Within 5 min after icv treatment, CRF, in a dose-related fashion, produced a significant increase in heart rate, core temperature, and behavioral activity. The absence of effect of 30 ng CRF, which already may be regarded as a supraphysiological amount, suggests that CRF does not modify ANS and behavioral activity under resting conditions. Tachycardiac responses in rats receiving 0.1-mu-g CRF, icv, in the morning were more marked than those in rats given the same treatment in the late afternoon. In addition, the presumed intrinsic activity of the CRF receptor antagonist, alpha-helical CRF-(9-41) (alpha-hCRF) at doses of 0.1, 1, 5, and 25-mu-g was evaluated. Intracerebroventricular injections of 0.1 and 1-mu-g alpha-hCRF failed to produce detectable effects. At the 5- and 25-mu-g doses, alpha-hCRF dose-dependently induced tachycardia and behavioral activation, suggesting partial agonistic activity. Taken together, these results demonstrate that CRF does not play a role in the regulation of ANS and behavioral activity under resting conditions. The responses produced by icv injected supraphysiological amounts of CRF, however, may serve to model a stressful situation during which the massively released CRF induces similar effects on ANS and behavior, after reaching high local concentrations at brain sites involved in the mediation of these actions.