Prolactin-releasing peptide (PrRP) reduces food intake and body weight, and modifies body temperature when administered centrally in rats, suggesting a role in energy homeostasis. However, the mediators of PrRP's action are unknown. The present study, therefore, firstly examined the possible involvement of the anorectic neuropeptides, corticotrophin-releasing hormone (CRH) and the melanocortins (e.g. -melanocyte stimulating hormone) in PrRP's effects on food intake and core body temperature, and secondly determined if PrRP affects energy expenditure by measuring oxygen consumption (VO₂). Intracerebroventricular (icv) injection of PrRP (4 nmol) to 24h fasted male Sprague-Dawley rats decreased food intake and modified body temperature. Blockade of central CRH receptors by icv co-administration of the CRH receptor antagonist, astressin (20 µg), reversed the PrRP-induced reduction in feeding. However, astressin's effect on PrRP-induced changes in body temperature was complicated, since the antagonist itself caused a slight rise in body temperature. In contrast, icv co-administration of the melanocortin receptor-3/4 antagonist, SHU9119 (0.1 nmol), had no effect on any of PrRP's actions. Finally, icv injection of PrRP (4 nmol) caused a significantly greater VO₂ over a 3 h test period compared with vehicle-treated rats. These results show that the anorectic actions of PrRP are mediated by central CRH receptors, but not by melanocortin receptors-3/4, and that PrRP can modify VO₂.