Operant, oral alcoholic beer self-administration by C57BL/6J mice: effect of BHF177, a positive allosteric modulator of GABAB receptors
Rationale With its high palatability, near-beer has been successfully used in rats as a vehicle to induce ethanol oral self-administration. Objectives The study aimed to develop an operant model of oral alcoholic beer self-administration promoting a stable intake of pharmacologically relevant amount...
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Published in | Psychopharmacologia Vol. 222; no. 4; pp. 685 - 700 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer-Verlag
01.08.2012
Springer |
Subjects | |
Online Access | Get full text |
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Summary: | Rationale
With its high palatability, near-beer has been successfully used in rats as a vehicle to induce ethanol oral self-administration.
Objectives
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.
Methods
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.
Results
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.
Conclusions
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. |
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ISSN: | 0033-3158 1432-2072 |
DOI: | 10.1007/s00213-012-2672-6 |