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Tiagabine does not attenuate alcohol-induced activation of the human reward system

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Abstract

Rationale

The rewarding effects of ethanol and other drugs of abuse are mediated by activation of the mesolimbic dopamine system. Recent neuroimaging studies in primates and humans suggest that cocaine-induced dopamine stimulation might be diminished by drugs augmenting γ-aminobutyric acid A (GABA-A) receptor function such as the GABA transaminase inhibitor vigabatrin.

Objectives

The objective of this study was to test the property of the selective GABA transporter 1 (GAT1) inhibitor tiagabine to block ethanol-induced activation of the mesolimbic reward system in an i.v. ethanol challenge.

Materials and methods

Twenty nonaddicted healthy volunteers underwent an i.v. ethanol challenge after 1 week of tiagabine (15 mg/day) administration. Neuronal activation was measured using [18F]-fluoro-deoxyglucose positron emission tomography (PET).

Results

Tiagabine did not prevent ethanol-induced stimulation of the mesolimbic reward system but augmented ethanol-induced hypometabolism within areas of the visual system and the cerebellum. Tiagabine alone also decreased neuronal metabolism within parts of the right temporal cortex that are highly enriched with GABA-ergic neurons.

Conclusions

Our ethanol challenge imaging study does not provide supporting evidence that the GAT1 inhibitor tiagabine diminishes the rewarding effects of ethanol. Further PET imaging studies using established anticraving compounds, such as the μ-opioid receptor antagonist naltrexone and antiepileptic drugs affecting the GABA-ergic system more broadly, will provide additional important insights on the interaction between the GABA-ergic and the brain reward system in vivo and the suitability of GABA-ergic drugs as anticraving compounds.

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Acknowledgment

This study was supported by the MAIFOR program of the University of Mainz. Some of the results of this article form a part of the physician’s thesis of the coauthor Natalie Chechko at the Medical Faculty of the Johannes Gutenberg-University Mainz, Germany. Furthermore, the authors thank Mrs. Uta Juergens, Epilepsy Research Center, Kehl-Kork, Germany, for measuring the tiagabine plasma levels.

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Authors and Affiliations

  1. Department of Psychiatry, University of Mainz, Untere Zahlbacher Strasse 8, 55131, Mainz, Germany

    Christoph Fehr, Nina Hohmann & Thomas F. Dielentheis

  2. Department of Psychiatry and Psychotherapy, RWTH Aachen University, Aachen, Germany

    Gerhard Gründer

  3. Department of Nuclear Medicine, University of Mainz, Mainz, Germany

    Hans-Georg Buchholz, Natalie Chechko, Igor Yakushev, Christian Landvogt, Peter Bartenstein & Mathias Schreckenberger

  4. Max Planck Institute for Psychiatry, Munich, Germany

    Natalie Chechko

  5. Department of Nuclear Medicine, University of Munich (LMU), Munich, Germany

    Peter Bartenstein

  6. Institute of Legal Medicine, University of Mainz, Mainz, Germany

    Reinhard Urban

Authors
  1. Christoph Fehr
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  2. Nina Hohmann
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  3. Gerhard Gründer
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  4. Thomas F. Dielentheis
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  5. Hans-Georg Buchholz
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  6. Natalie Chechko
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  7. Igor Yakushev
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  8. Christian Landvogt
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  9. Peter Bartenstein
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  10. Reinhard Urban
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  11. Mathias Schreckenberger
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Correspondence to Christoph Fehr.

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Fehr, C., Hohmann, N., Gründer, G. et al. Tiagabine does not attenuate alcohol-induced activation of the human reward system. Psychopharmacology 191, 975–983 (2007). https://doi.org/10.1007/s00213-006-0696-5

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  • DOI: https://doi.org/10.1007/s00213-006-0696-5

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