title: Ethanol-related behaviors in mice lacking the sigma-1 receptor.
abstract: BACKGROUND
  The Sigma-1 receptor (Sig-1R) is a chaperone protein that has been implicated in drug abuse and addiction. Multiple studies have characterized the role the Sig-1R plays in psychostimulant addiction; however, fewer studies have specifically investigated its role in alcohol addiction. We have previously shown that antagonism of the Sig-1R reduces excessive drinking and motivation to drink, whereas agonism induces binge-like drinking in rodents.
  
  
  OBJECTIVE
  The objectives of these studies were to investigate the impact of Sig-1R gene deletion in C57Bl/6J mice on ethanol drinking and other ethanol-related behaviors.
  
  
  METHODS
  We used an extensive panel of behavioral tests to examine ethanol actions in male, adult mice lacking Oprs1, the gene encoding the Sig-1R. To compare ethanol drinking behavior, Sig-1 knockout (KO) and wild type (WT) mice were subject to a two-bottle choice, continuous access paradigm with different concentrations of ethanol (3-20% v/v) vs. water. Consumption of sweet and bitter solutions was also assessed in Sig-1R KO and WT mice. Finally, motor stimulant sensitivity, taste aversion and ataxic effects of ethanol were assessed.
  
  
  RESULTS
  Sig-1R KO mice displayed higher ethanol intake compared to WT mice; the two genotypes did not differ in their sweet or bitter taste perception. Sig-1R KO mice showed lower sensitivity to ethanol stimulant effects, but greater sensitivity to its taste aversive effects. Ethanol-induced sedation was instead unaltered in the mutants.
  
  
  CONCLUSIONS
  Our results prove that the deletion of the Sig-1R increases ethanol consumption, likely by decreasing its rewarding effects, and therefore indicating that the Sig-1R is involved in modulation of the reinforcing effects of alcohol.
authors.affiliation: Laboratory of Addictive Disorders, Departments of Pharmacology and Psychiatry, Boston University School of Medicine, Boston, MA, United States; Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Valenza
authors.affiliation: Laboratory of Addictive Disorders, Departments of Pharmacology and Psychiatry, Boston University School of Medicine, Boston, MA, United States.
authors.forename: Alyssa
authors.initials: A
authors.lastname: DiLeo
authors.affiliation: Department of Physiology and Pharmacology "V. Erspamer", Sapienza University, Rome, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Steardo
authors.affiliation: Laboratory of Addictive Disorders, Departments of Pharmacology and Psychiatry, Boston University School of Medicine, Boston, MA, United States.
authors.forename: Pietro
authors.initials: P
authors.lastname: Cottone
authors.affiliation: Laboratory of Addictive Disorders, Departments of Pharmacology and Psychiatry, Boston University School of Medicine, Boston, MA, United States. Electronic address: vsabino@bu.edu.
authors.forename: Valentina
authors.initials: V
authors.lastname: Sabino
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism*; D019973:Alcohol-Related Disorders / Q000378:metabolism*; D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000378:metabolism; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017480:Receptors, sigma / Q000235:genetics / Q000378:metabolism*; D013649:Taste / Q000187:drug effects / Q000502:physiology; D055697:Taste Perception / Q000187:drug effects / Q000502:physiology; D000097605:Sigma-1 Receptor
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor
keywords: Addiction; Consumption; Drinking; Mutant; Oprs1; Reinforcement