title: (R)-Salsolinol, a product of ethanol metabolism, stereospecifically induces behavioral sensitization and leads to excessive alcohol intake.
abstract: Ethanol is oxidized in the brain to acetaldehyde, which can condense with dopamine to generate (R/S)-salsolinol [(RS)-SAL]. Racemic salsolinol [(RS)-SAL] is self-infused by rats into the posterior ventral tegmental area (VTA) at significantly lower concentrations than those of acetaldehyde, suggesting that (RS)-SAL is a most active product of ethanol metabolism. Early studies showed that repeated intraperitoneal or intra-VTA administration of (RS)-SAL (10 mg/kg) induced conditioned place preference, led to locomotor sensitization and increased voluntary ethanol consumption. In the present study, we separated the (R)- and (S)-enantiomers from a commercial (RS)-SAL using a high-performance liquid chromatography with electrochemical detection system fitted with a β-cyclodextrin-modified column. We injected (R)-SAL or (S)-SAL (30 pmol/1.0 μl) into the VTA of naïve UChB rats bred as alcohol drinkers to study whether one or both SAL enantiomers are responsible for the motivated behavioral effects, sensitization and increase in voluntary ethanol intake. The present results show that repeated administration of (R)-SAL leads to (1) conditioned place preference; (2) locomotor sensitization; and (3) marked increases in binge-like ethanol intake. Conversely, (S)-SAL did not influence any of these parameters. Overall, data indicate that (R)-SAL stereospecifically induces motivational effects, behavioral sensitization and increases ethanol intake.
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, University of Chile, Chile. equintanilla@med.uchile.cl.
authors.forename: María Elena
authors.initials: ME
authors.lastname: Quintanilla
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, University of Chile, Chile.|Millennium Institute BNI, Faculty of Medicine, University of Chile, Chile.
authors.forename: Mario
authors.initials: M
authors.lastname: Rivera-Meza
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, University of Chile, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Berríos-Cárcamo
authors.affiliation: Department of Chemistry, Faculty of Sciences, University of Chile, Chile.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Cassels
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, University of Chile, Chile.|Millennium Institute BNI, Faculty of Medicine, University of Chile, Chile.
authors.forename: Mario
authors.initials: M
authors.lastname: Herrera-Marschitz
authors.affiliation: Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, University of Chile, Chile.
authors.forename: Yedy
authors.initials: Y
authors.lastname: Israel
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage / Q000378:metabolism; D005260:Female; D006702:Homing Behavior / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D009042:Motivation / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D017208:Rats, Wistar
chemical_list: D007546:Isoquinolines; D000431:Ethanol; C036617:salsolinol
keywords: (R)-salsolinol; (RS)-salsolinol; (S)-salsolinol; Ethanol; motivation; sensitization