Chronic intracerebroventricular CRF infusion attenuates ACTH-corticosterone release

Bolus intracerebroventricular delivery of corticotropin-releasing factor (CRF) elicits acute responses of both the pituitary-adrenal axis and the sympathetic nervous system. We examined whether these stresslike responses could be maintained over a period of days by central delivery of CRF in nonstressed rats, as would be predicted if this peptide participates in the central nervous system regulation of chronic stress. CRF (4.3 or 21.5 micrograms/day) was continuously delivered into the cerebral ventricle via Alzet minipumps. In contrast to saline-infused controls, rats receiving CRF exhibited elevated excretions of corticosterone, norepinephrine, and urea nitrogen for several days. Thereafter, an attenuation of CRF responsiveness occurred when corticosterone excretion returned to basal levels despite continued central CRF infusion. However, CRF delivered intravenously during attenuation stimulated adrenocorticotropic hormone and corticosterone secretion, implicating a hypothalamic rather than pituitary locus for central CRF resistance. The present data do not permit a conclusion on whether the attenuation of the CRF response with time is the result of an ultrashort-loop negative-feedback mechanism or CRF receptor desensitization.