Central Actions of Corticotropin-Releasing Hormone (CRH) on Behavioral, Neuroendocrine, and Cardiovascular Regulation:Brain Corticoid Receptor Involvement

The effect of intracerebroventricularly (icv) infused corticotropin-releasing hormone (CRH), 300 ng, infused at a rate of 16.67 ng/min during 18 min and its relation to the functioning of brain corticoid receptors was investigated in freely moving rats in their home cages. Behavior was sampled before, during, and after the CRH infusion. Cardiovascular measurements were made via a chronically implanted catheter in the descending aorta. Blood samples were withdrawn to determine adrenal hormone concentration. Central administration of the brain mineralocorticoid-like receptor (MR) antagonist (RU 28318, 100 ng) and the glucocorticoid receptor (GR) antagonist (RU 38486, 100 ng) 60 min before CRH infusion served to manipulate adrenal steroid states in the brain. CRH infusion caused behavioral activation which was associated with an increase in heart rate (HR) and mean arterial blood pressure (MAP). Increased plasma corticosterone and norepinephrine levels were observed, while a minor elevation of epinephrine (E) levels also occurred. Both corticoid receptor antagonists failed to affect the CRH-induced behavioral activation. Administration of the GR antagonist significantly enhanced the magnitude of the CRH-induced increase in E, whereas the effect of the MR antagonist just failed to reach significance. These findings suggest the involvement of central corticoid receptors in sympathoadrenomedullary feedback mechanisms. The MR antagonist elevated baseline MAP probably thereby suppressing the magnitude of the CRH response. The increase in HR was diminished by both antagonists shortly after CRH infusion. Together, the data suggest involvement of brain corticosteroid receptor-mediated processes in neuroendocrine and cardiovascular effects of CRH