title: Relaxin-3 receptor (RXFP3) signalling mediates stress-related alcohol preference in mice.
abstract: Stressful life events are causally linked with alcohol use disorders (AUDs), providing support for a hypothesis that alcohol consumption is aimed at stress reduction. We have previously shown that expression of relaxin-3 mRNA in rat brain correlates with alcohol intake and that central antagonism of relaxin-3 receptors (RXFP3) prevents stress-induced reinstatement of alcohol-seeking. Therefore the objectives of these studies were to investigate the impact of Rxfp3 gene deletion in C57BL/6J mice on baseline and stress-related alcohol consumption. Male wild-type (WT) and Rxfp3 knockout (KO) (C57/B6JRXFP3TM1/DGen) littermate mice were tested for baseline saccharin and alcohol consumption and preference over water in a continuous access two-bottle free-choice paradigm. Another cohort of mice was subjected to repeated restraint followed by swim stress to examine stress-related alcohol preference. Hepatic alcohol and aldehyde dehydrogenase activity was assessed in mice following chronic alcohol intake and in naive controls. WT and Rxfp3 KO mice had similar baseline saccharin and alcohol preference, and hepatic alcohol processing. However, Rxfp3 KO mice displayed a stress-induced reduction in alcohol preference that was not observed in WT littermates. Notably, this phenotype, once established, persisted for at least six weeks after cessation of stress exposure. These findings suggest that in mice, relaxin-3/RXFP3 signalling is involved in maintaining high alcohol preference during and after stress, but does not appear to strongly regulate the primary reinforcing effects of alcohol.
authors: Neuropeptides Division, The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia; Behavioural Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
authors: Andrew W
authors: AW
authors: Walker
authors: Neuropeptides Division, The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia; Behavioural Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
authors: Craig M
authors: CM
authors: Smith
authors: Neuropeptides Division, The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia.
authors: Berenice E
authors: BE
authors: Chua
authors: Behavioural Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia.
authors: Elena V
authors: EV
authors: Krstew
authors: Neuropeptides Division, The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
authors: Cary
authors: C
authors: Zhang
authors: Neuropeptides Division, The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia; Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia.
authors: Andrew L
authors: AL
authors: Gundlach
authors: Behavioural Neuroscience Division, The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia; Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
authors: Andrew J
authors: AJ
authors: Lawrence
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000428:Alcohol Drinking; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D000431:Ethanol / Q000378:metabolism; D005247:Feeding Behavior / Q000502:physiology*; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012439:Saccharin; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D043562:Receptors, G-Protein-Coupled; C505050:SALPR protein, mouse; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D012439:Saccharin