Cortical gamma-aminobutyric acid type A-benzodiazepine receptors in recovery from alcohol dependence: relationship to features of alcohol dependence and cigarette smoking.
BACKGROUND
Adaptations in gamma-aminobutyric acid type A (GABA(A))-benzodiazepine receptors contribute to the neurobiology of human alcohol dependence and withdrawal.


OBJECTIVE
To study GABA(A)-benzodiazepine receptor adaptations in subjects with alcohol dependence over the first month of sobriety.


METHODS
Inpatients who were not receiving medication, were either smokers or nonsmokers, and had alcohol dependence completed 2 iodine I 123-labeled iomazenil single-photon emission computed tomographic scans: 1 scan at a mean +/- SD of 4.9 +/- 2.5 days of sobriety (n = 23) and 1 scan at a mean +/- SD of 29.8 +/- 7.6 days of sobriety (n = 20). Participants in a matched group of healthy subjects (n = 15) completed 1 single-photon emission computed tomographic scan.


METHODS
Men with alcohol dependence (n = 27) and a matched healthy comparison group (n = 15).


METHODS
(123)I-iomazenil single-photon emission computed tomographic images were converted to units of distribution volume (regional activity/free (123)I-iomazenil) and were analyzed using voxel-based statistical parametric mapping and regions of interest analyses. The relationships between (123)I-iomazenil distribution volume, clinical features of alcohol dependence, and smoking status were evaluated.


RESULTS
(123)I-iomazenil uptake was elevated in several cortical regions, with a more prominent increase in nonsmokers with alcohol dependence as compared with smokers with alcohol dependence at 1 week of abstinence from alcohol. No significant differences were observed at 4 weeks of abstinence. At 1 week of abstinence, frontal (123)I-iomazenil uptake correlated with the severity of alcohol withdrawal and the number of days since the last alcoholic drink was consumed. No significant associations were observed for smokers with alcohol dependence.


CONCLUSIONS
These data demonstrate time-dependent regulation of cortical GABA(A)-benzodiazepine receptors associated with the recovery from alcohol dependence. Higher GABA(A)-benzodiazepine receptor levels during acute withdrawal may reflect a compensation for reduced receptor function, which is thought to contribute to alcohol tolerance and withdrawal. The subsequent decline may reflect "normalization" of GABA(A) receptor function with sobriety. Smoking may attenuate GABA(A) receptor adaptations associated with alcohol dependence and may contribute to the comorbidity between alcoholism and smoking.
Staley
Julie K
JK
Yale University School of Medicine, 950 Campbell Avenue, New Haven, CT 06516, USA. julie.staley@yale.edu
Gottschalk
Christopher
C
Petrakis
Ismene L
IL
Gueorguieva
Ralitza
R
O'Malley
Stephanie
S
Baldwin
Ronald
R
Jatlow
Peter
P
Verhoeff
Nicolaas Paul L G
NP
Perry
Edward
E
Weinzimmer
David
D
Frohlich
Erin
E
Ruff
Elizabeth
E
van Dyck
Christopher H
CH
Seibyl
John P
JP
Innis
Robert B
RB
Krystal
John H
JH
D000328:Adult; D000437:Alcoholism / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000378:metabolism*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism*; D015897:Comorbidity; D000431:Ethanol / Q000009:adverse effects; D005442:Flumazenil / Q000031:analogs & derivatives*; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D011963:Receptors, GABA-A / Q000032:analysis* / Q000378:metabolism; D012907:Smoking / Q000453:epidemiology / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control; D013695:Temperance; D015899:Tomography, Emission-Computed, Single-Photon
D007457:Iodine Radioisotopes; D011963:Receptors, GABA-A; D000431:Ethanol; D005442:Flumazenil; C063038:iomazenil