Differential behavioral actions of corticotropin-releasing factor (CRF).

In order to elucidate the involvement of the 41 amino-acid residue corticotropin-releasing factor (CRF) in the modulation of brain functioning, the behavioral profile of the releasing hormone was determined using tests for spontaneous behavior, grooming, active and passive avoidance behavior. Intracerebroventricular (ICV) administration of CRF in a dose that does not stimulate the pituitary-adrenal axis, resulted in an activation of open-field behavior, as measured by ambulation and rearing activities. Also grooming activity was significantly enhanced after central application of CRF. In hypophysectomized rats, which show an impaired shuttle-box avoidance acquisition, CRF restored acquisition for the duration of the treatment. Paradoxically, extinction of pole-jumping active avoidance behavior of intact rats was facilitated by the releasing factor, even in adrenalectomized animals. Passive avoidance behavior was affected bidirectional: higher doses of CRF (300 ng), given subcutaneously (SC), attenuated passive avoidance retention, probably via activation of the pituitary-adrenal system resulting in high corticosterone levels. Lower doses (30 ng), however, which were also given SC did not stimulate pituitary-adrenal activity, and facilitated retention of passive avoidance behavior. Central administration of CRF in very low doses (30 pg) had the same effect as higher doses of CRF given SC, i.e., inhibition of passive avoidance retention. Taken together, the data indicate that CRF can affect behavior via a direct action on the central nervous system. The question remains whether this activity is an intrinsic property of CRF, or mediated by the release of hormones or neuropeptides.