Tiagabine does not attenuate alcohol-induced activation of the human reward system.
BACKGROUND
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 gamma-aminobutyric acid A (GABA-A) receptor function such as the GABA transaminase inhibitor vigabatrin.


OBJECTIVE
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.


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 [(18)F]-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 mu-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.
Fehr
Christoph
C
Department of Psychiatry, University of Mainz, Untere Zahlbacher Strasse 8, 55131, Mainz, Germany. fehrc@uni-mainz.de
Hohmann
Nina
N
Gründer
Gerhard
G
Dielentheis
Thomas F
TF
Buchholz
Hans-Georg
HG
Chechko
Natalie
N
Yakushev
Igor
I
Landvogt
Christian
C
Bartenstein
Peter
P
Urban
Reinhard
R
Schreckenberger
Mathias
M
D000328:Adult; D016739:Behavior, Addictive / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology*; D019788:Fluorodeoxyglucose F18; D050485:GABA Plasma Membrane Transport Proteins / Q000378:metabolism; D058805:GABA Uptake Inhibitors; D006801:Humans; D008032:Limbic System / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009557:Nipecotic Acids / Q000494:pharmacology*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals; D012016:Reference Values; D012201:Reward; D016037:Single-Blind Method; D000078308:Tiagabine; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002492:Central Nervous System Depressants; D050485:GABA Plasma Membrane Transport Proteins; D058805:GABA Uptake Inhibitors; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D019275:Radiopharmaceuticals; C493413:SLC6A1 protein, human; D019788:Fluorodeoxyglucose F18; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D000078308:Tiagabine