Ability of Baclofen in Reducing Alcohol Intake and Withdrawal Severity: I—Preclinical Evidence

Authors

  • Giancarlo Colombo,

    Corresponding author
    1. CNR Center for Neuropharmacology, Cagliari (G.C., G.L.G.); Bernard B. Brodie Department of Neuroscience, University of Cagliari, Cagliari (R.A., M.A.M.C., C.L., M.P.); Neuroscienze S.c.ar.l., Cagliari (M.A.M.C., G.L.G., C.L., R.R.); and Institute of Internal Medicine, Catholic University, Rome, Italy (G.A.).
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  • Roberta Agabio,

    1. CNR Center for Neuropharmacology, Cagliari (G.C., G.L.G.); Bernard B. Brodie Department of Neuroscience, University of Cagliari, Cagliari (R.A., M.A.M.C., C.L., M.P.); Neuroscienze S.c.ar.l., Cagliari (M.A.M.C., G.L.G., C.L., R.R.); and Institute of Internal Medicine, Catholic University, Rome, Italy (G.A.).
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  • Mauro A.M. Carai,

    1. CNR Center for Neuropharmacology, Cagliari (G.C., G.L.G.); Bernard B. Brodie Department of Neuroscience, University of Cagliari, Cagliari (R.A., M.A.M.C., C.L., M.P.); Neuroscienze S.c.ar.l., Cagliari (M.A.M.C., G.L.G., C.L., R.R.); and Institute of Internal Medicine, Catholic University, Rome, Italy (G.A.).
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  • Carla Lobina,

    1. CNR Center for Neuropharmacology, Cagliari (G.C., G.L.G.); Bernard B. Brodie Department of Neuroscience, University of Cagliari, Cagliari (R.A., M.A.M.C., C.L., M.P.); Neuroscienze S.c.ar.l., Cagliari (M.A.M.C., G.L.G., C.L., R.R.); and Institute of Internal Medicine, Catholic University, Rome, Italy (G.A.).
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  • Marialaura Pani,

    1. CNR Center for Neuropharmacology, Cagliari (G.C., G.L.G.); Bernard B. Brodie Department of Neuroscience, University of Cagliari, Cagliari (R.A., M.A.M.C., C.L., M.P.); Neuroscienze S.c.ar.l., Cagliari (M.A.M.C., G.L.G., C.L., R.R.); and Institute of Internal Medicine, Catholic University, Rome, Italy (G.A.).
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  • Roberta Reali,

    1. CNR Center for Neuropharmacology, Cagliari (G.C., G.L.G.); Bernard B. Brodie Department of Neuroscience, University of Cagliari, Cagliari (R.A., M.A.M.C., C.L., M.P.); Neuroscienze S.c.ar.l., Cagliari (M.A.M.C., G.L.G., C.L., R.R.); and Institute of Internal Medicine, Catholic University, Rome, Italy (G.A.).
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  • Giovanni Addolorato,

    1. CNR Center for Neuropharmacology, Cagliari (G.C., G.L.G.); Bernard B. Brodie Department of Neuroscience, University of Cagliari, Cagliari (R.A., M.A.M.C., C.L., M.P.); Neuroscienze S.c.ar.l., Cagliari (M.A.M.C., G.L.G., C.L., R.R.); and Institute of Internal Medicine, Catholic University, Rome, Italy (G.A.).
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  • Gian Luigi Gessa

    1. CNR Center for Neuropharmacology, Cagliari (G.C., G.L.G.); Bernard B. Brodie Department of Neuroscience, University of Cagliari, Cagliari (R.A., M.A.M.C., C.L., M.P.); Neuroscienze S.c.ar.l., Cagliari (M.A.M.C., G.L.G., C.L., R.R.); and Institute of Internal Medicine, Catholic University, Rome, Italy (G.A.).
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  • The present study was partially supported by the European Community, the Italian Government, and the Regione Autonoma della Sardegna through Programma Operativo Plurifondo—Sardegna.

Reprint requests: Giancarlo Colombo, PhD, CNR Center for Neuropharmacology, Bernard B. Brodie Department of Neuroscience, University of Cagliari, Via Porcell 4, I-09124 Cagliari, Italy; Fax: 39–070–657–237; E-mail: colomb@unica.it

Abstract

Background:

The similarities between the pharmacological effects of the γ-aminobutyric acid receptor agonist, baclofen, and the alcohol-substituting agent, γ-hydroxybutyric acid, led us to investigate whether baclofen was capable of reducing (a) ethanol withdrawal syndrome in ethanol-dependent rats and (b) voluntary ethanol intake in ethanol-preferring rats.

Methods:

In experiment 1, Wistar rats were rendered physically dependent on ethanol by the repeated administration of intoxicating doses of ethanol for 6 consecutive days. Baclofen was acutely administered intraperitoneally at doses of 10, 20, and 40 mg/kg. In experiment 2, baclofen (0, 2.5, 5, and 10 mg/kg, intraperitoneally) was administered once a day for 14 consecutive days to ethanol-preferring sP rats that had continuous access to ethanol (10%, v/v) and water under the two-bottle free choice regimen.

Results:

In experiment 1, baclofen dose-dependently decreased the intensity of ethanol withdrawal signs; furthermore, 20 mg/kg of baclofen protected from audiogenic seizures in ethanol-withdrawn rats. In experiment 2, baclofen selectively and dose-dependently reduced voluntary ethanol intake; a compensatory increase in water intake left total fluid intake virtually unchanged.

Conclusions:

These results are in close agreement with those of a preliminary clinical study and suggest that baclofen may constitute a novel therapeutic agent for alcoholism.

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