Tiagabine does not attenuate alcohol-induced activation of the human reward system
Psychopharmacology
Volume 191, Number 4 / May, 2007
p. 975-983
Christoph Fehr Email: fehrc@uni-mainz.de
Nina Hohmann1, G
Gerhard Gründer2,
Thomas F. Dielentheis1,
Hans-Georg Buchholz3,
Natalie Chechko3, 4,
Igor Yakushev3,
Christian Landvogt3,
Peter Bartenstein3, 5,
Reinhard Urban6 and
Mathias Schreckenberger3
| (1) | Department of Psychiatry, University of Mainz, Untere Zahlbacher Strasse 8, 55131 Mainz, Germany |
| (2) | Department of Psychiatry and Psychotherapy, RWTH Aachen University, Aachen, Germany |
| (3) | Department of Nuclear Medicine, University of Mainz, Mainz, Germany |
| (4) | Max Planck Institute for Psychiatry, Munich, Germany |
| (5) | Department of Nuclear Medicine, University of Munich (LMU), Munich, Germany |
| (6) | Institute of Legal Medicine, University of Mainz, Mainz, Germany |
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.
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.
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.
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.
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.
Keywords Tiagabine - GABA - Alcohol - Ethanol - Striatum - Imaging - PET - 18-FDG
 | Christoph Fehr Email: fehrc@uni-mainz.de |
