The role of the CRH type 1 receptor in autonomic responses to corticotropin-releasing hormone in the rat

The involvement of the corticotopin-releasing hormone (CRH) type 1 receptor in CRH-induced cardiac responses was studied in freely moving rats. Intrac erebroventricular (icv) infusion of 2 mu g CRH under resting conditions res ulted in a significant increase in heart rate (HR), but did not significant ly affect the PQ interval of the electrocardiogram. This effect involves sy mpathetic nervous system (SNS) activation, since CRH-treatment resulted in a market increase in plasma norepinephrine (NE) and epinephrine (E), and sy mpathetic blockade by subcutaneously injected atenolol (1 mg/kg), a beta 1- selective adrenergic antagonist, completely prevented the CRH-induced tachy cardia. CRH infusion after sympathetic blockade resulted in an elongation o f the PQ interval, indicating CRH-induced vagal activation. Gross locomotor activity (GA) was determined to study its possible indirect effects on car diac activity. Although CRH induced a marked increase in GA, this effect fo llowed the tachycardiac response, indicating that the HR response was not a consequence of increased locomotor activity, but was a direct effect of ic v CRH. Treatment with CP-154,526 (icv, 10 or 25 mu g), a selective CRH type 1 receptor antagonist, did not affect baseline HR, plasma NE and E, wherea s it partially blocked the CRH-induced increase in HR, plasma NE and E leve ls. CP-154,526 treatment had no significant effects on baseline or CRH-indu ced changes in GA. These results system at least in part via the CRH type 1 receptor. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.