Long-term effects on feeding and body weight after stimulation of forebrain or hindbrain CRH receptors with urocortin

Research on the contribution of CRH receptor stimulation to energy homeosta sis has focused on forebrain substrates. In this study, we explored the eff ects of caudal brainstem administration of the CRH receptor agonist, urocor tin, on food intake and body weight, and on plasma glucose and corticostero ne (CORT) in non-deprived rats. Urocortin (0, 0.3, 1, 3 mu g) delivered, re spectively, to the fourth and lateral ventricles yielded substantial suppre ssion of food intake measured 2, 4 and 24 h later. A significant but more m odest anorexia was observed between 24 and 48 h after injection. Intake res ponses did not differ between the injection sites, but body weight loss mea sured 24 h after lateral-i.c.v. injection was substantially greater than th at after fourth-i.c.v. injection. Fourth-i.c.v. urocortin adminjstration (3 mu g) produced substantial elevations in plasma glucose and CORT that were not distinguishable in magnitude and duration from responses to lateral-i. c.v. delivery. Unilateral microinjection of urocortin into the dorsal vagal complex significantly reduced 24-h food intake at a dose (0.1 mu g) that w as subthreshold for the response to ventricular administration, suggesting that fourth-i.c.v. effects are mediated in part by stimulation of CRH recep tors in this region of the caudal brainstem. The results indicate that simi lar effects can be obtained from stimulation of anatomically disparate popu lations of CRH receptors, and that interactions between forebrain and hindb rain structures should be considered in the evaluation of CRH contributions to food intake and body weight control. (C) 2000 Elsevier Science B.V. All rights reserved.