The hindbrain is a site of energy balance action for prolactin-releasing peptide: feeding and thermic effects from GPR10 stimulation of the nucleus tractus solitarius/area postrema

• Published in: Psychopharmacology 2018-08, Vol.235 (8), p.2287-2301
• Main Authors: Davis, X. S., Grill, H. J.
• Format: Article
• Language: English
• Subjects: Animals; Appetite (Psychophysiology); Area postrema; Area Postrema - drug effects; Area Postrema - metabolism; Biomedical and Life Sciences; Biomedicine; Body temperature; Body Temperature - drug effects; Body Temperature - physiology; Body weight; Body Weight - drug effects; Body Weight - physiology; Brain research; Dose-Response Relationship, Drug; Eating - drug effects; Eating - physiology; Energy balance; Feeding; Feeding behavior; Food intake; Forebrain; Hindbrain; Male; Microinjections - methods; Motivation; Neuropeptides; Neurosciences; Original Investigation; Pharmacology/Toxicology; Prolactin; Prolactin-Releasing Hormone - administration & dosage; Prolactin-releasing peptide; Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled - agonists; Receptors, G-Protein-Coupled - metabolism; Rhombencephalon; Rodents; Solitary Nucleus - drug effects; Solitary Nucleus - metabolism; Solitary tract nucleus; Temperature effects; Ventricle; Ventricles (cerebral); Weight loss
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-018-4925-5

Purpose Prolactin-releasing peptide (PrRP) is a neuropeptide that suppresses food intake and increases body temperature when delivered to the forebrain ventricularly or parenchymally. However, PrRP’s receptor GPR10 is widely distributed throughout the brain with particularly high levels found in the dorsomedial hindbrain. Thus, we hypothesized that hindbrain-directed PrRP administration would affect energy balance and motivated feeding behavior. Methods To address this hypothesis, a range of behavioral and physiologic variables were measured in Sprague-Dawley rats that received PrRP delivered to the fourth ventricle (4V) or the nucleus of the solitary tract (NTS) at the level of the area postrema (AP). Results 4V PrRP delivery decreased chow intake and body weight, in part, through decreasing meal size in ad libitum maintained rats tested at dark onset. PrRP inhibited feeding when delivered to the nucleus tractus solitarius (NTS), but not to more ventral hindbrain structures. In addition, 4V as well as direct NTS administration of PrRP increased core temperature. By contrast, 4V PrRP did not reduce ad libitum intake of highly palatable food or the motivation to work for or seek palatable foods. Conclusions The dorsomedial hindbrain and NTS/AP, in particular, are sites of action in PrRP/GPR10-mediated control of chow intake, core temperature, and body weight.