Marta Valenza1, Alyssa DiLeo2, Luca Steardo3, Pietro Cottone2, Valentina Sabino4. 1. 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. 2. Laboratory of Addictive Disorders, Departments of Pharmacology and Psychiatry, Boston University School of Medicine, Boston, MA, United States. 3. Department of Physiology and Pharmacology "V. Erspamer", Sapienza University, Rome, Italy. 4. Laboratory of Addictive Disorders, Departments of Pharmacology and Psychiatry, Boston University School of Medicine, Boston, MA, United States. Electronic address: vsabino@bu.edu.
Abstract
RATIONALE: 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. OBJECTIVES: 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.
RATIONALE: 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. OBJECTIVES: 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: Angelo Blasio; Marta Valenza; Malliga R Iyer; Kenner C Rice; Luca Steardo; T Hayashi; Pietro Cottone; Valentina Sabino Journal: Behav Brain Res Date: 2015-04-04 Impact factor: 3.332
Authors: Valentina Sabino; Pietro Cottone; Angelo Blasio; Malliga R Iyer; Luca Steardo; Kenner C Rice; Bruno Conti; George F Koob; Eric P Zorrilla Journal: Neuropsychopharmacology Date: 2011-02-23 Impact factor: 7.853
Authors: Catherine F Moore; Julia I Panciera; Valentina Sabino; Pietro Cottone Journal: Philos Trans R Soc Lond B Biol Sci Date: 2018-03-19 Impact factor: 6.237
Authors: Margaret A Minnig; Tayun Park; Maria Echeveste Sanchez; Pietro Cottone; Valentina Sabino Journal: Front Behav Neurosci Date: 2021-12-03 Impact factor: 3.617