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The Effects of Ghrelin Antagonists [ D ‐ L ys 3 ]‐ GHRP ‐6 or JMV 2959 on Ethanol, Water, and Food Intake in C57BL/6J Mice
Author(s) -
Gomez Juan L.,
Ryabinin Andrey E.
Publication year - 2014
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.12499
Subject(s) - ghrelin , medicine , antagonist , ethanol , endocrinology , zoology , food intake , chemistry , receptor , biochemistry , biology
Background Alcohol use and abuse patterns have created a need for novel treatment models. Current research has turned its focus on reward pathways associated with intrinsic necessities, such as feeding. Theories suggest that drugs of abuse seize control of natural reward pathways and dysregulate normal function, leading to chronic addiction. One such pathway involving the hunger stimulating peptide, ghrelin, is the focus of our study. Methods Male C57BL/6J mice were randomly assigned to groups and treated with vehicle or a ghrelin antagonist, either [D‐Lys 3 ]‐ GHRP ‐6 ( DL ys) or JMV 2959. Three experiments tested ghrelin antagonism using different doses; experiment 1 tested 12 mg/kg JMV 2959; experiment 2 tested 15 mg/kg DL ys; experiment 3 tested 9 mg/kg JMV 2959. Using a 2‐bottle choice 24‐hour access paradigm, data were collected for ethanol intake, preference, water intake, and food intake at 4 and 24 hours after injection. Results Experiment 1 showed that 12 mg/kg of JMV 2959 decreased ethanol, water, and food intake, without affecting preference. Experiment 2 showed that 15 mg/kg of DL ys decreased ethanol intake, preference, and water intake only on the first day of treatment. Experiment 3 showed that 9 mg/kg of JMV 2959 decreased only ethanol and food intake. No change was seen during deprivation, and JMV 2959 was still effective at reducing ethanol intake upon reintroduction. Despite the change in food intake, there were no differences in body weight throughout the experiments. It should be noted that the majority of significant effects were only found 4 hours postinjection. Conclusions The results show that compounds that block ghrelin receptor activity are effective at decreasing ethanol intake. However, DL ys was only effective at reducing intake and preference on the first day, suggesting a quick tolerance and selectivity for ethanol. JMV 2959 consistently reduced ethanol intake, but at the higher dose also reduced all other consummatory behaviors. Thus, ghrelin antagonists provide a viable potential for treatment of alcohol abuse disorders, but further research is needed to determine an appropriate dose and administration paradigm.