title: Relaxin-3/RXFP3 system regulates alcohol-seeking.
abstract: Relapse and hazardous drinking represent the most difficult clinical problems in treating patients with alcohol use disorders. Using a rat model of alcohol use and alcohol-seeking, we demonstrated that central administration of peptide antagonists for relaxin family peptide 3 receptor (RXFP3), the cognate receptor for the highly conserved neuropeptide, relaxin-3, decreased self-administration of alcohol in a dose-related manner and attenuated cue- and stress-induced reinstatement following extinction. By comparison, RXFP3 antagonist treatment did not significantly attenuate self-administration or reinstatement of sucrose-seeking, suggesting a selective effect for alcohol. RXFP3 is densely expressed in the stress-responsive bed nucleus of the stria terminalis, and bilateral injections of RXFP3 antagonist into the bed nucleus of the stria terminalis significantly decreased self-administration and stress-induced reinstatement of alcohol, suggesting that this brain region may, at least in part, mediate the effects of RXFP3 antagonism. RXFP3 antagonist treatment had no effect on general ingestive behavior, activity, or procedural memory for lever pressing in the paradigms assessed. These data suggest that relaxin-3/RXFP3 signaling regulates alcohol intake and relapse-like behavior, adding to current knowledge of the brain chemistry of reward-seeking.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, Department of Anatomy and Neuroscience, and School of Chemistry, The University of Melbourne, VIC 3010, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Ryan
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Kastman
authors.forename: Elena V
authors.initials: EV
authors.lastname: Krstew
authors.forename: K Johan
authors.initials: KJ
authors.lastname: Rosengren
authors.forename: Mohammed Akhter
authors.initials: MA
authors.lastname: Hossain
authors.forename: Leonid
authors.initials: L
authors.lastname: Churilov
authors.forename: John D
authors.initials: JD
authors.lastname: Wade
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Gundlach
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lawrence
mesh_terms: D000437:Alcoholism / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D008568:Memory / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D012008:Recurrence; D012065:Relaxin / Q000378:metabolism*; D012686:Septal Nuclei / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013395:Sucrose / Q000494:pharmacology; D013549:Sweetening Agents / Q000494:pharmacology
chemical_list: C577472:RXFP3 protein, rat; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D013549:Sweetening Agents; D013395:Sucrose; D012065:Relaxin
keywords: addiction; dependence