Work

Lateral hypothalamic melanocortin receptor signaling modulates binge-like ethanol drinking in C57BL/6J mice

Year: 2015

Type: article

Abstract: Binge ethanol drinking is a highly pervasive and destructive behavior yet the underlying neurobiological mechanisms remain poorly understood. Recent work suggests that overlapping neurobiological mechanisms modulate feeding disorders and excessive ethanol intake, and converging evidence indicates that the melanocortin (MC) system may be a promising candidate. The aims of the present work were to examine how repeated binge-like ethanol drinking, using the 'drinking in the dark' (DID) protocol, impacts key peptides within the MC system and if site-specific manipulation of MC receptor (MCR) signaling modulates binge-like ethanol drinking. Male C57BL/6J mice were exposed to one, three or six cycles of binge-like ethanol, sucrose or water drinking, after which brain tissue was processed via immunohistochemistry (IHC) for analysis of key MC peptides, including alpha-melanocyte stimulating hormone (α-MSH) and agouti-related protein (AgRP). Results indicated that α-MSH expression was selectively decreased, while AgRP expression was selectively increased, within specific hypothalamic subregions following repeated binge-like ethanol drinking. To further explore this relationship, we used site-directed drug delivery techniques to agonize or antagonize MCRs within the lateral hypothalamus (LH). We found that the nonselective MCR agonist melanotan-II (MTII) blunted, while the nonselective MCR antagonist AgRP augmented, binge-like ethanol consumption when delivered into the LH. As these effects were region-specific, the present results suggest that a more thorough understanding of the MC neurocircuitry within the hypothalamus will help provide novel insight into the mechanisms that modulate excessive binge-like ethanol intake and may help uncover new therapeutic targets aimed at treating alcohol abuse disorders.

Source: Addiction Biology

DOI: 10.1111/adb.12264

Authors: Gretchen M. Sprow, Jennifer A. Rinker, Emily G. Lowery-Gointa, Angela M. Sparrow, Montserrat Navarro, Todd E. Thiele

Institution: University of North Carolina at Chapel Hill

Language: English

Topic: Regulation of Appetite and Obesity

Subfield: Endocrine and Autonomic Systems

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: U.S. Department of Defense, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse