title: Alcohol-preferring AA rats show a derangement in their central melanocortin signalling system.
abstract: The AA (Alko, Alcohol) rats are selectively bred for their preference of alcohol to water, contrasting to ANA rats that avoid alcohol. They also exhibit a lower growth rate compared to ANA rats, as well as differences in their response to substances affecting food intake. The melanocortin (MC) system is involved in the regulation of feeding behaviour and in mechanisms underlying drug addiction and tolerance. Recently, administration of an MC receptor agonist proved to reduce alcohol intake in AA rats. We predicted that the ratio of endogenous MC receptor agonists (proopiomelanocortin, POMC) and antagonists (agouti-related protein, AgRP) would differ from ANA rats, and that subsequent differences in MC receptor levels would be detectable. We used in situ hybridization to detect an increased ratio of POMC/AgRP mRNA in the arcuate nucleus (Arc) of AA rats. Receptor autoradiography indicated that MC3 receptor binding differed in the nucleus accumbens and several hypothalamic nuclei, possibly reflecting differences in MC peptide transmission in the AA rats. Our results support the claim that AA rats have a high ratio of POMC/AgRP expression, and that this observation is accompanied by differences in MC3 receptor levels.
authors.affiliation: Division of Pharmacology, Department of Pharmaceutical Biosciences, Uppsala University, BMC, Box 591, S-751 24 Uppsala, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Lindblom
authors.forename: J E S
authors.initials: JE
authors.lastname: Wikberg
authors.forename: L
authors.initials: L
authors.lastname: Bergström
mesh_terms: D054369:Agouti-Related Protein; D000428:Alcohol Drinking / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000502:physiology; D002755:Choice Behavior / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D018043:Receptors, Corticotropin / Q000235:genetics / Q000502:physiology*; D044101:Receptors, Melanocortin; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D011333:Pro-Opiomelanocortin