INTRACEREBROVENTRICULAR INJECTION OF CORTICOTROPIN-RELEASING HORMONE IN THE PIG - ACUTE EFFECTS ON BEHAVIOR, ADRENOCORTICOTROPIN SECRETION,AND IMMUNE SUPPRESSION

Corticotropin-releasing hormone (CRH) has been implicated as an import ant mediator of behavior, immune, and neuroendocrine systems in animal s experiencing stress, but its effects on these systems have not been evaluated in an integrated whole animal model. In this experiment we i njected porcine and rat CRH (pCRH and rCRH) intracerebroventricularly (icv) and simultaneously and chronologically monitored acute changes i n behavior, endocrine, and immune function in the pig. PBS or CRH (15, 50, and 150 mu g pCRH and 15 and 150 mu g rCRH) was injected icv, and serial blood samples were collected via an indwelling jugular cathete r so that behavior could be monitored simultaneously. The central admi nistration of pCRH and rCRH induced immediate dose-dependent behaviora l and physiological responses. Pigs receiving 15 mu g of either pCRH o r rCRH had increased plasma ACTH and were hyperactive and vocal. Howev er, when higher doses (i.e. 50 or 150 mu g) were administered icv, the endocrine and behavioral responses were accompanied by a profound sup pression of Concanavalin-A-induced lymphocyte proliferation. For examp le, pigs receiving 150 mu g pCRH had increased plasma ACTH and motor a ctivity at 10 min (P < 0.01) and suppressed lymphocyte proliferation a t 30 min (P < 0.001). Whereas ACTH secretion declined after 40 min, th e lymphocyte suppression and increased motor activity were sustained, suggesting different control mechanisms. It is suggested that although ACTH and cortisol may have negative feedback effects on ACTH secretio n, they did not have these effects on the behavioral action of CRH. Fu rthermore, although the lowest dose of CRH (15 mu g) induced motor act ivity and ACTH secretion, higher doses (50 or 150 mu g) were necessary for suppression of mitogen-induced lymphocyte proliferation. These fi ndings demonstrate that CRH in the pig brain is active for inducing si multaneous changes in behavioral and physiological systems and are, th erefore, consistent with the hypothesis that brain CRH is important in mediating the interaction among behavior, endocrine, and immune syste ms in animals experiencing stress.