The RFamides are so called because they all have common C-terminal arginine and phenylalanine residues. Through evolution, they have had a role in feeding behaviour and, in rodents, brainstem neurones containing one RFamide, prolactin-releasing peptide (PrRP), mediate the effects of the gut-brain satiety signalling. Thus, PrRP can mimic satiation and reduction in gastric emptying, whilst the actions of cholecystokinin are absent in mice lacking either PrRP or its receptor (GPR10). Both of these transgenic models display late-onset obesity. However, GPR10 receptor knock-out mice are obese primarily because they display lower than normal energy expenditure. In this study, we use mice fitted with intraperitoneal radiotelemetric devices and with indwelling lateral ventricular cannulae. Surgery is carried out under general inhalation anaesthesia (2% isoflurane in 1L/min oxygen). Animals are given an intraperitoneal (i.p.) injection of 0.01mg kg-1 buprenorphine before recovery and maintained at 37oC for four hours post surgery. Animals remained singly housed post surgery, and were monitored daily for 7 days before further procedures were carried out. Intracerebroventricular injection of PrRP (4 nmol) increases both energy expenditure and core-body-temperature in wild-type, but not in GPR10 knock-out mice (analysis of variance with Bonferroni post hoc tests used in all analyses). When later kept at a lower ambient temperature (15oC for five days), the mice maintain their core-body temperature by shivering, as they are unable to activate brown adipose tissue (BAT), even though their BAT has thermogenic capacity. Similarly, the mice cannot initiate non-shivering thermogenesis in response to leptin (5 mg/kg, i.p.). We have demonstrated that a population of PrRP neurones in the dorsomedial nucleus of the hypothalamus, are an integral part of the central circuitry involved in sympathetic activation of brown adipose tissue.