Cortical gamma-aminobutyric acid levels and the recovery from ethanol dependence: preliminary evidence of modification by cigarette smoking.
BACKGROUND
Gamma-aminobutyric acid (GABA)ergic adaptations contribute to the neurobiology of ethanol dependence and withdrawal. Clinical data suggest that tobacco smoking attenuates alcohol withdrawal symptoms. This study's objective was to measure time-dependent cortical GABA levels with sobriety in ethanol-dependent patients with mild to moderate withdrawal severity, controlling for alcoholism-related neurotoxicity and smoking.


METHODS
Proton magnetic resonance spectroscopy (MRS) was used to measure occipital cortical N-acetylaspartate (NAA), glutamate plus glutamine, and GABA in 12 ethanol-dependent men at approximately 1 week and 1 month of medication-free sobriety on an inpatient unit. Eight healthy men were studied once. The tissue composition of the MRS volume was determined.


RESULTS
Adjusting for less white matter in patients, GABA differed insignificantly between ethanol-dependent patients (smokers plus nonsmokers) and healthy subjects. In early sobriety, nonsmoking patients had more GABA than did smoking patients, but by 1 month, GABA decreased in nonsmokers without changing in smokers. Smoking was associated with increased glutamate plus glutamine in patients and healthy subjects, adjusting for NAA levels.


CONCLUSIONS
These data do not show that deficits in cortical GABA contribute directly to acute ethanol withdrawal. If smoking prevents withdrawal-related changes in cortical GABA systems, it may contribute to comorbidity of alcoholism and tobacco smoking.
Mason
Graeme F
GF
NIAAA Center for the Translational Neuroscience of Alcoholism and Department of Psychiatry, Yale University, School of Medicine, New Haven, CT 06520, USA. graeme.mason@yale.edu
Petrakis
Ismene L
IL
de Graaf
Robin A
RA
Gueorguieva
Ralitza
R
Guidone
Elizabeth
E
Coric
Vladimir
V
Epperson
C Neill
CN
Rothman
Douglas L
DL
Krystal
John H
JH
D000328:Adult; D000437:Alcoholism / Q000378:metabolism* / Q000628:therapy; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009778:Occipital Lobe / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline