Physiological and behavioral effects of chronic intracerebroventricular infusion of corticotropin-releasing factor in the rat.

The present study was conducted to investigate the long-term effects of chronic elevation of centrally circulating levels of corticotropin-releasing factor (CRF) on behavior and physiology. For this purpose ovine CRF was infused continuously for a period of 10 days into the lateral ventricle of rats with the aid of osmotic pumps (calculated CRF delivery was 4.9 micrograms/day). Changes in daily rhythms in body temperature and home cage motor activity were recorded telemetrically during the infusion period. The most prominent physiological findings were a delayed body weight gain and a long-lasting hyperthermia following CRF infusion. The peptide treatment furthermore increased adrenal weight and suppressed the weight of the thymus at the end of the experiment. Behaviorally, CRF administration elicited a short-lasting increase in activity during the light phase and an increased anxiety in an elevated plus-maze 1 week after the start of infusion. The similarities between the present results and the long-term changes previously described in behaviorally stressed rats indicate that chronically elevated levels of CRF in the brain might play an important role in the induction and persistence of stress-related behavioral and physiological disorders.