Effect of Agouti-related protein delivered to the dorsomedial nucleus of the hypothalamus on intake of a preferred versus a non-preferred diet

• Published in: Brain research Vol. 897; no. 1; pp. 169 - 174
• Main Authors: Wirth, Michelle M, Giraudo, Silvia Q
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 06-04-2001; Amsterdam Elsevier; New York, NY
• Subjects: Agouti-Related Protein; Animal Feed; Animals; Biological and medical sciences; Dietary Sucrose; Dorsomedial Hypothalamic Nucleus - drug effects; Dorsomedial Hypothalamic Nucleus - physiology; Dorsomedial nucleus of the hypothalamus; Eating - drug effects; Feeding. Feeding behavior; Food intake; Food preference; Food Preferences - drug effects; Fundamental and applied biological sciences. Psychology; Intercellular Signaling Peptides and Proteins; Male; Melanocortin; Melanocortin-4 receptor; Microinjections; Proteins - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4; Receptors, Corticotropin - antagonists & inhibitors; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Zea mays; Agouti-related protein; Melanocortin-4 receptor; Dorsomedial nucleus of the hypothalamus; Food intake; Melanocortin; Neural basic of behavior; Food preference; Agonist; Rat; Rodentia; Central nervous system; Dorsomedial nucleus; Hypothalamus; Feeding preference; Feeding; Vertebrata; Mammalia; MC4 melanocortin receptor; Diet; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(01)02087-X

Agouti-related protein (Agrp), a high-affinity antagonist of the melanocortin-3/4 receptors, increases feeding when administered centrally. Previous studies have shown that this increase is long-lasting (at least 24 h) and delayed, unless the animal is first stimulated to feed by fasting or onset of the dark phase. The present studies first demonstrate that long-lasting and delayed increases in food intake are also evident when Agrp is microinjected into the dorsomedial nucleus of the hypothalamus (DMH). Next, the effects of DMH-administered Agrp were assessed on intake of two foods, isocaloric but differing in flavor (with or without sucrose). Following exposure to the two diets, rats were injected via cannula aimed at the DMH with 100 pmol Agrp at 10:00 h and allowed ad libitum access to either: (1) a choice of both diets or (2) one of the diets alone. Food intake was determined at 2, 4, and 24 h post-injection. In the first (choice) paradigm, Agrp only increased intake of the sucrose-containing diet. In the second (no-choice) paradigm, animals on either diet showed an Agrp-induced increase in intake 24 h following injection; only animals on the sucrose-containing diet showed an increase in intake 4 h post-injection. The results are discussed in the context of the possible involvement of Agrp/MC4-R in the rewarding characteristics of food intake.