Ghrelin receptor deletion reduces binge-like alcohol drinking in rats. 2019

Lia J Zallar, and Silvia Beurmann, and Brendan J Tunstall, and Claire M Fraser, and George F Koob, and Leandro F Vendruscolo, and Lorenzo Leggio
Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, and National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Bethesda, Maryland.

Ghrelin is a gastric hormone that has been implicated in the neurobiology of alcohol drinking. We have recently developed a ghrelin receptor (growth hormone secretagogue receptor; GHSR) knockout (KO) rat model, which exhibits reduced food consumption and body weight. In addition, recent preliminary work suggests that the gut-microbiome, which appears to interact with the ghrelin system, may modulate alcohol drinking. In the present study, we investigated the effects of GHSR deletion on alcohol consumption utilising GHSR KO and wild-type (WT) rats in three separate alcohol consumption paradigms: (i) operant self-administration (30-minute sessions); (ii) drinking in the dark (DID) (4-hour sessions); and (iii) intermittent access (24-hour sessions). These paradigms model varying degrees of alcohol consumption. Furthermore, we aimed to investigate the gut-microbiome composition of GHSR KO and WT rats before and after alcohol exposure. We found that the GHSR KO rats self-administered significantly less alcohol compared to WT rats in the operant paradigm, and consumed less alcohol than WT in the initial stages of the DID paradigm. No genotype differences were found in the intermittent access test. In addition, we found a significant decrease in gut-microbial diversity after alcohol exposure in both genotypes. Thus, the present results indicate that the ghrelin system may be involved in drinking patterns that result in presumably increased alcohol exposure levels. Furthermore, GHSR may constitute a potential pharmacological target for the reduction of binge-alcohol consumption. The potential functional role of the gut-microbiome in alcohol drinking, as well as interaction with the ghrelin system, is an interesting topic for further investigation.

UI MeSH Term Description Entries
D003216 Conditioning, Operant Learning situations in which the sequence responses of the subject are instrumental in producing reinforcement. When the correct response occurs, which involves the selection from among a repertoire of responses, the subject is immediately reinforced. Instrumental Learning,Learning, Instrumental,Operant Conditioning,Conditionings, Operant,Instrumental Learnings,Learnings, Instrumental,Operant Conditionings
D000069196 Gastrointestinal Microbiome All of the microbial organisms that naturally exist within the GASTROINTESTINAL TRACT. Enteric Bacteria,Gastric Microbiome,Gastrointestinal Flora,Gastrointestinal Microbial Community,Gastrointestinal Microbiota,Gastrointestinal Microflora,Gut Flora,Gut Microbiome,Gut Microbiota,Gut Microflora,Intestinal Flora,Intestinal Microbiome,Intestinal Microbiota,Intestinal Microflora,Bacteria, Enteric,Flora, Gastrointestinal,Flora, Gut,Flora, Intestinal,Gastric Microbiomes,Gastrointestinal Microbial Communities,Gastrointestinal Microbiomes,Gastrointestinal Microbiotas,Gut Microbiomes,Gut Microbiotas,Intestinal Microbiomes,Intestinal Microbiotas,Microbial Community, Gastrointestinal,Microbiome, Gastric,Microbiome, Gastrointestinal,Microbiome, Gut,Microbiome, Intestinal,Microbiota, Gastrointestinal,Microbiota, Gut,Microbiota, Intestinal,Microflora, Gastrointestinal,Microflora, Gut,Microflora, Intestinal
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D054440 Receptors, Ghrelin Transmembrane proteins that recognize and bind GHRELIN, a potent stimulator of GROWTH HORMONE secretion and food intake in mammals. Ghrelin receptors are found in the pituitary and HYPOTHALAMUS. They belong to the family of G-PROTEIN-COUPLED RECEPTORS. Growth Hormone Secretagogue Receptor,Growth Hormone Secretagogue Receptors,GHS Receptor Type 1,GHS-R Type 1A,GHS-R1A,GHS-R1B,GHSR Protein,Ghrelin Receptor,Growth Hormone Secretagogue Receptor Type 1,Growth Hormone Secretagogue Receptor Type 1A,Growth Hormone Secretagogue Receptor Type 1B,Growth Hormone Secretogogue Receptor 1B,Receptor, Growth Hormone Secretagogue 1A,GHS R Type 1A,Ghrelin Receptors,Receptor, Ghrelin
D055786 Gene Knockout Techniques Techniques to alter a gene sequence that result in an inactivated gene, or one in which the expression can be inactivated at a chosen time during development to study the loss of function of a gene. Gene Knock-Out Techniques,Gene Knock Out,Gene Knock Out Techniques,Gene Knockout,Gene Knock Outs,Gene Knock-Out Technique,Gene Knockout Technique,Gene Knockouts,Knock Out, Gene,Knock Outs, Gene,Knock-Out Technique, Gene,Knock-Out Techniques, Gene,Knockout Technique, Gene,Knockout Techniques, Gene,Knockout, Gene,Knockouts, Gene,Out, Gene Knock,Outs, Gene Knock,Technique, Gene Knock-Out,Technique, Gene Knockout,Techniques, Gene Knock-Out,Techniques, Gene Knockout
D058999 Drug-Seeking Behavior Activities performed to obtain licit or illicit substances. Behavior, Drug-Seeking,Behaviors, Drug-Seeking,Drug Seeking Behavior,Drug-Seeking Behaviors
D063425 Binge Drinking Drinking an excessive amount of ALCOHOLIC BEVERAGES in a short period of time. Binge Alcohol Consumption,Alcohol Consumption, Binge,Drinking, Binge

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