Intracerebroventricular injection of corticotropin-releasing hormone in the pig: acute effects on behavior, adrenocorticotropin secretion, and immune suppression.

ABSTRACT

Corticotropin-releasing hormone (CRH) has been implicated as an important mediator of behavior, immune, and neuroendocrine systems in animals experiencing stress, but its effects on these systems have not been evaluated in an integrated whole animal model. In this experiment we injected porcine and rat CRH (pCRH and rCRH) intracerebroventricularly (icv) and simultaneously and chronologically monitored acute changes in behavior, endocrine, and immune function in the pig. PBS or CRH (15, 50, and 150 micrograms pCRH and 15 and 150 micrograms rCRH) was injected icv, and serial blood samples were collected via an indwelling jugular catheter so that behavior could be monitored simultaneously. The central administration of pCRH and rCRH induced immediate dose-dependent behavioral and physiological responses. Pigs receiving 15 micrograms of either pCRH or rCRH had increased plasma ACTH and were hyperactive and vocal. However, when higher doses (i.e. 50 or 150 micrograms) were administered icv, the endocrine and behavioral responses were accompanied by a profound suppression of Concanavalin-A-induced lymphocyte proliferation. For example, pigs receiving 150 micrograms pCRH had increased plasma ACTH and motor activity at 10 min (P < 0.01) and suppressed lymphocyte proliferation at 30 min (P < 0.001). Whereas ACTH secretion declined after 40 min, the 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 secretion, they did not have these effects on the behavioral action of CRH. Furthermore, although the lowest dose of CRH (15 micrograms) induced motor activity and ACTH secretion, higher doses (50 or 150 micrograms) were necessary for suppression of mitogen-induced lymphocyte proliferation. These findings demonstrate that CRH in the pig brain is active for inducing simultaneous changes in behavioral and physiological systems and are, therefore, consistent with the hypothesis that brain CRH is important in mediating the interaction among behavior, endocrine, and immune systems in animals experiencing stress.