Relaxin-3 receptor (Rxfp3) gene deletion reduces operant sucrose- but not alcohol-responding in mice.
The pervasive use of refined sugars in highly accessible, palatable foods and persistent exposure to reinforcing food-associated cues has contributed to overconsumption of sugar-rich diets and the current obesity epidemic in Western society. We have shown previously that brain relaxin-3 mRNA levels positively correlate with sucrose and alcohol intake, and that central antagonism of relaxin-3 receptors (RXFP3) attenuates alcohol self-administration and alcohol-seeking in rats, but food-seeking behaviour and palatable food consumption in mice. To further examine the relationship between motivated appetitive behaviours and relaxin-3/RXFP3 signalling, we investigated the effect of Rxfp3 gene deletion in C57BL/6J mice on sucrose and alcohol self-administration and cue-induced reinstatement (RNST) of sucrose- and alcohol-seeking. Acquisition and maintenance of sucrose and alcohol self-administration was assessed in male wild-type (WT) and Rxfp3 knockout (KO) (C57BL/6J(RXFP3TM1) (/) (DGen) ) littermate mice using fixed ratio (FR) schedules of reinforcement. Mice were subsequently challenged with a progressive ratio (PR) test to measure motivation and, following extinction training, re-exposed to reward-associated cues to evaluate RNST of active lever-responding. Wild-type and Rxfp3 KO mice displayed similar acquisition of FR1 sucrose self-administration, but Rxfp3 KO mice responded less when the instrumental requirement was increased to FR3. These mice also showed a lower breakpoint for sucrose and attenuated cue-induced RNST of sucrose-seeking. Notably, no marked genotype differences in alcohol-responding were observed. In mice, endogenous relaxin-3/RXFP3 signalling promotes self-administration of sucrose under high response requirements and cue-induced RNST of sucrose-seeking, but does not apparently regulate motivation to consume alcohol or alcohol-seeking behaviour.
The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia.|Florey Department of Neuroscience and Mental Health, Melbourne, Victoria, Australia.
A W
AW
Walker
The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia.|Florey Department of Neuroscience and Mental Health, Melbourne, Victoria, Australia.
C M
CM
Smith
The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia.|Florey Department of Neuroscience and Mental Health, Melbourne, Victoria, Australia.|Department of Anatomy and Neuroscience, The University of Melbourne, Melbourne, Victoria, Australia.
A L
AL
Gundlach
The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia.|Florey Department of Neuroscience and Mental Health, Melbourne, Victoria, Australia.
A J
AJ
Lawrence
D000428:Alcohol Drinking / Q000235:genetics; D000818:Animals; D001070:Appetitive Behavior / Q000502:physiology; D003216:Conditioning, Operant / Q000502:physiology*; D000431:Ethanol / Q000008:administration & dosage*; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009042:Motivation / Q000235:genetics / Q000502:physiology; D011897:Random Allocation; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012065:Relaxin / Q000172:deficiency* / Q000235:genetics; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage*
D043562:Receptors, G-Protein-Coupled; C512898:relaxin-3 protein, mouse; D000431:Ethanol; D013395:Sucrose; D012065:Relaxin
Alcohol; cue-induced reinstatement; operant; progressive ratio; relaxin-3/RXFP3; sucrose-seeking