Effect of Agouti-related protein delivered to the dorsomedial nucleus of the hypothalamus on intake of a preferred versus a non-preferred diet.
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.
Research Service 151, Minneapolis Veterans Affairs Medical Center, 1 Veterans Drive, Minneapolis, MN 55417, USA.
M M
MM
Wirth
S Q
SQ
Giraudo
D054369:Agouti-Related Protein; D000821:Animal Feed; D000818:Animals; D019422:Dietary Sucrose; D004302:Dorsomedial Hypothalamic Nucleus / Q000187:drug effects* / Q000502:physiology*; D004435:Eating / Q000187:drug effects*; D005518:Food Preferences / Q000187:drug effects*; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008845:Microinjections; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000037:antagonists & inhibitors; D003313:Zea mays
C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D019422:Dietary Sucrose; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin