title: Effects of DA-Phen, a dopamine-aminoacidic conjugate, on alcohol intake and forced abstinence.
abstract: The mesolimbic dopamine (DA) system plays a key role in drug reinforcement and is involved in the development of alcohol addiction. Manipulation of the DAergic system represents a promising strategy to control drug-seeking behavior. Previous studies on 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-Phen) showed in vivo effects as a DA-ergic modulator. This study was aimed at investigate DA-Phen effects on operant behavior for alcohol seeking behavior, during reinstatement following subsequent periods of alcohol deprivation. For this purpose, male Wistar rats were tested in an operant paradigm of self-administration; behavioral reactivity and anxiety like-behavior during acute abstinence were evaluated. A characterization of DA-Phen CNS targeting by its quantification in the brain was also carried out. Our findings showed that DA-Phen administration was able to reduce relapse in alcohol drinking by 50% and reversed the alterations in behavioral reactivity and emotionality observed during acute abstinence. In conclusion, DA-Phen can reduce reinstatement of alcohol drinking in an operant-drinking paradigm following deprivation periods and reverse abstinence-induced behavioral phenotype. DA-Phen activity seems to be mediated by the modulation of the DAergic transmission. However further studies are needed to characterize DA-Phen pharmacodynamic and pharmacokinetic properties, and its potential therapeutic profile in alcohol addiction.
authors.affiliation: Department of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Flavia Maria
authors.initials: FM
authors.lastname: Sutera
authors.affiliation: Department of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: De Caro
authors.affiliation: Department of Sciences for Health Promotion and Mother and Child Care "Giuseppe D'Alessandro", University of Palermo, Via del Vespro 133, 90127 Palermo, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Cannizzaro
authors.affiliation: Department of Biological Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Libero Italo
authors.initials: LI
authors.lastname: Giannola
authors.affiliation: Department of Sciences for Health Promotion and Mother and Child Care "Giuseppe D'Alessandro", University of Palermo, Via del Vespro 133, 90127 Palermo, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Lavanco
authors.affiliation: Department of Sciences for Health Promotion and Mother and Child Care "Giuseppe D'Alessandro", University of Palermo, Via del Vespro 133, 90127 Palermo, Italy. Electronic address: fulvio.plescia@unipa.it.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Plescia
mesh_terms: D000427:Alcohol Deterrents / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000188:drug therapy / Q000378:metabolism; D000437:Alcoholism / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000008:administration & dosage; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D058999:Drug-Seeking Behavior / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage; D008297:Male; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017208:Rats, Wistar; D012008:Recurrence; D012646:Self Administration
chemical_list: C553723:2-amino-N-(2-(3,4-dihydroxyphenyl)ethyl)-3-phenylpropionamide; D000427:Alcohol Deterrents; D002492:Central Nervous System Depressants; D015259:Dopamine Agents; D000431:Ethanol; D010649:Phenylalanine; D004298:Dopamine
keywords: Addiction; CNS targeting; Dopamine derivatives; Dopaminergic neurotransmission; Operant self-administration paradigm