title: Cortical gamma-aminobutyric acid type A-benzodiazepine receptors in recovery from alcohol dependence: relationship to features of alcohol dependence and cigarette smoking.
abstract: 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.
authors.affiliation: Yale University School of Medicine, 950 Campbell Avenue, New Haven, CT 06516, USA. julie.staley@yale.edu
authors.forename: Julie K
authors.initials: JK
authors.lastname: Staley
authors.forename: Christopher
authors.initials: C
authors.lastname: Gottschalk
authors.forename: Ismene L
authors.initials: IL
authors.lastname: Petrakis
authors.forename: Ralitza
authors.initials: R
authors.lastname: Gueorguieva
authors.forename: Stephanie
authors.initials: S
authors.lastname: O'Malley
authors.forename: Ronald
authors.initials: R
authors.lastname: Baldwin
authors.forename: Peter
authors.initials: P
authors.lastname: Jatlow
authors.forename: Nicolaas Paul L G
authors.initials: NP
authors.lastname: Verhoeff
authors.forename: Edward
authors.initials: E
authors.lastname: Perry
authors.forename: David
authors.initials: D
authors.lastname: Weinzimmer
authors.forename: Erin
authors.initials: E
authors.lastname: Frohlich
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ruff
authors.forename: Christopher H
authors.initials: CH
authors.lastname: van Dyck
authors.forename: John P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: Robert B
authors.initials: RB
authors.lastname: Innis
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
mesh_terms: 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
chemical_list: D007457:Iodine Radioisotopes; D011963:Receptors, GABA-A; D000431:Ethanol; D005442:Flumazenil; C063038:iomazenil