Operant, oral alcoholic beer self-administration by C57BL/6J mice: effect of BHF177, a positive allosteric modulator of GABA(B) receptors

• Published in: Psychopharmacology (Berlin, Germany) Vol. 222; no. 4; p. 685
• Main Authors: Orrù, Alessandro, Fujani, Daniele, Cassina, Chiara, Conti, Mirko, Di Clemente, Angelo, Cervo, Luigi
• Format: Journal Article
• Language: English
• Published: Germany 01.08.2012
• Subjects: Allosteric Regulation - drug effects; Animals; Baclofen - pharmacology; Beer; Conditioning, Operant - drug effects; Dose-Response Relationship, Drug; Ethanol - administration & dosage; Ethanol - pharmacology; GABA-B Receptor Agonists - pharmacology; Male; Maze Learning - drug effects; Mice; Mice, Inbred C57BL; Models, Animal; Motor Activity - drug effects; Norbornanes - pharmacology; Pyrimidines - pharmacology; Reinforcement Schedule; Rotarod Performance Test - methods; Self Administration - methods
• ISSN: 1432-2072
• DOI: 10.1007/s00213-012-2672-6

With its high palatability, near-beer has been successfully used in rats as a vehicle to induce ethanol oral self-administration. The study aimed to develop an operant model of oral alcoholic beer self-administration promoting a stable intake of pharmacologically relevant amounts of ethanol in free-feeding C57BL/6J mice. It also aimed to assess the model's predictive validity by evaluating the influence of baclofen, a GABA(B) agonist, and BHF177, a GABA(B) positive allosteric modulator, on alcoholic beer self-administration. Mice were trained to self-administer, under a fixed ratio three schedule of reinforcement, 10 μl of beer containing increasing ethanol concentrations (0-18% v/v) in daily 30-min sessions. The effects on motor coordination (rotarod), locomotor activity (open field, automated cages) and anxiety-like behavior (elevated plus maze, EPM) were examined. Baclofen (1.25-5 mg/kg, intraperitoneal, i.p.) and BHF177 (3.75-30 mg/kg, i.p.) were used to see the effects on 9% alcoholic beer and near-beer self-administration. Near-beer stably maintained operant oral self-administration in mice. Adding ethanol to near-beer reduced the number of active lever presses, while the corresponding amount of ethanol self-administration increased (0.8-1.0 g/kg/session). Motor impairment was observed when more than 1.3 g/kg/session of ethanol was self-administered with beer and slight but consistent hyperlocomotion with more than 0.9-1.0 g/kg/session. BHF177 (15 mg/kg) preferentially reduced 9% alcoholic beer self-administration, while the higher dose (30 mg/kg)-like baclofen 5 mg/kg-also reduced near-beer self-administration. The operant model of oral alcoholic beer self-administration in C57BL/6J mice should prove useful for studying ethanol-reinforced behaviors and to identify candidate compounds for the pharmacological management of alcohol addiction.