Differential dose effects of central CRF and effects of CRF astressin on pig behavior.

Abstract

The elevation of central corticotropin releasing factor (CRF) causes an increase in behavioral activity, including increases in overall activity and oral/nasal/facial (ONF) chewing-rooting-rubbing behaviors in the pig and similar behaviors in other species. This study detailed changes in the frequency, duration and sequences of behaviors after central administration of vehicle or porcine CRF (pCRF at 0.5, 5.0, 50 and 150 microg). A sequential analysis described the complex behaviors induced in a dose-dependent fashion by central pCRF. The frequency and duration of ONF behaviors were significantly increased among pigs receiving 50 microg of pCRF. For behaviors such as ONF, 50 microg represented a breakpoint at which the frequency and duration of single behaviors increased. Pigs receiving 50 microg of pCRF were considerably more active and exhibited more ONF behaviors than did pigs receiving lower doses. The highly sensitive sequential analysis revealed that very low doses of central pCRF induced subtle changes in sequences of behaviors. Low doses of central pCRF (0.5 microg) induced fear-related behavioral sequences that included ONF behaviors alternating with periods of inactivity. Central injection of astressin, a CRF receptor antagonist, blocked many, but not all, of CRF-induced behaviors. Compared with saline-injected control pigs, central pCRF increased general activity, ONF, fear-related freezing and sham chewing behaviors. When pCRF was given following astressin, fear-related freezing behaviors were not different compared with pigs receiving saline. However, pigs given astressin plus pCRF showed elevated sham chewing compared with saline-injected control pigs, as did pigs receiving intracerebroventricular (ICV) pCRF. These data indicate that central pCRF activates brain mechanisms associated with hyperactivity, ONF and fear-related behaviors, whereas other behaviors induced by pCRF may be nonspecifically mediated by CRF. Astressin antagonized some, but not all, pCRF-induced behaviors. This model represents the induction of hyperactivity and stereotyped behaviors, which may represent a new model for the study of mania or obsessive-compulsive behaviors.