Baclofen decreases compulsive alcohol drinking in rats characterized by reduced levels of GAT‐3 in the central amygdala

Autor: Aude Belin-Rauscent, Maxime Fouyssac, Lucía Martí-Prats, Paul J. Cocker, David Belin, Barry J. Everitt, Mickaёl Puaud
Přispěvatelé: Marti‐Prats, Lucia [0000-0003-2026-871X], Fouyssac, Maxime [0000-0002-9496-5836], Belin, David [0000-0002-7383-372X], Apollo - University of Cambridge Repository, Marti-Prats, Lucia [0000-0003-2026-871X]
Rok vydání: 2021
Předmět:
Male
Polymers
GABA transporter GAT‐3
Medicine (miscellaneous)
Self Administration
Alcohol
Alcohol use disorder
Rats
Sprague-Dawley
chemistry.chemical_compound
0302 clinical medicine
GABA transporter GAT-3
media_common
Quinine
alcohol
compulsive alcohol drinking
Alcoholism
Psychiatry and Mental health
medicine.anatomical_structure
Baclofen
Compulsive Behavior
Reinforcement
Psychology
Agonist
medicine.medical_specialty
medicine.drug_class
media_common.quotation_subject
baclofen
GABAB receptor
Amygdala
03 medical and health sciences
PRECLINICAL STUDIES
Internal medicine
medicine
Animals
Saccharin
ORIGINAL ARTICLE
Pharmacology
Ethanol
business.industry
Addiction
Central Amygdaloid Nucleus
medicine.disease
Rats
030227 psychiatry
Endocrinology
chemistry
nervous system
Endophenotype
central amygdala
Conditioning
Operant
business
030217 neurology & neurosurgery
Zdroj: Addiction Biology
DOI: 10.17863/cam.71783
Popis: While most individuals with access to alcohol drink it recreationally, some vulnerable individuals eventually lose control over their intake and progressively develop compulsive alcohol drinking and decreased interest in alternative sources of reinforcement, two key features of addiction. The neural and molecular mechanisms underlying this vulnerability to switch from controlled to compulsive alcohol intake have not been fully elucidated. It has been shown that rats having reduced levels of expression of the gamma‐aminobutyric acid (GABA) transporter, GAT‐3, in the amygdala tend to persist in seeking and drinking alcohol even when adulterated with quinine, suggesting that pharmacological interventions aimed at restoring GABA homeostasis in these individuals may provide a targeted treatment to limit compulsive alcohol drinking. Here, we tested the hypothesis that the GABAB receptor agonist baclofen, which decreases GABA release, specifically reduces compulsive alcohol drinking in vulnerable individuals. In a large cohort of Sprague–Dawley rats allowed to drink alcohol under an intermittent two‐bottle choice procedure, a cluster of individuals was identified that persisted in drinking alcohol despite adulteration with quinine or when an alternative ingestive reinforcer, saccharin, was available. In these rats, which were characterized by decreased GAT‐3 mRNA levels in the central amygdala, acute baclofen administration (1.5 mg/kg, intraperitoneal) resulted in a decrease in compulsive drinking. These results indicate that low GAT‐3 mRNA levels in the central amygdala may represent an endophenotype of vulnerability to develop a compulsive drinking of alcohol that is shown here to be mitigated by baclofen.
In a large cohort of rats allowed to drink alcohol under an intermittent two‐bottle choice procedure, a cluster of individuals was identified that persisted in drinking alcohol despite adulteration or the availability of an alternative ingestive reinforcer, saccharin. In these rats, that were characterized by decreased GAT‐3 mRNA levels in the central amygdala, acute baclofen administration resulted in a decrease in compulsive alcohol drinking.
Databáze: OpenAIRE
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