title: Cocaine abusers show a blunted response to alcohol intoxication in limbic brain regions.
abstract: Cocaine and alcohol are frequently used simultaneously and this combination is associated with enhanced toxicity. We recently showed that active cocaine abusers have a markedly enhanced sensitivity to benzodiazepines. Because both benzodiazepines and alcohol facilitate GABAergic neurotransmission we questioned whether cocaine abusers would also have an enhanced sensitivity to alcohol that could contribute to the toxicity. In this study we compared the effects of alcohol (0.75 g/kg) on regional brain glucose metabolism between cocaine abusers (n = 9) and controls (n = 10) using PET and FDG. Alcohol significantly decreased whole brain metabolism and this effect was greater in controls (26+/-6%) than in abusers (17+/-10%) even though they had equivalent levels of alcohol in plasma. Analysis of the regional measures showed that cocaine abusers had a blunted response to alcohol in limbic regions, cingulate gyrus, medial frontal and orbitofrontal cortices.
  
  
  CONCLUSIONS
  The blunted response to alcohol in cocaine abusers contrasts with their enhanced sensitivity to benzodiazepines suggesting that targets other than GABA-benzodiazepine receptors are involved in the blunted sensitivity to alcohol and that the toxicity from combined cocaine-alcohol use is not due to an enhanced sensitivity to alcohol in cocaine abusers. The blunted response to alcohol in limbic regions and in cortical regions connected to limbic areas could result from a decreased sensitivity of reward circuits in cocaine abusers.
authors.affiliation: Brookhaven National Laboratory, Upton, New York 11973, USA. volkow@bnl.gov
authors.forename: N D
authors.initials: ND
authors.lastname: Volkow
authors.forename: G J
authors.initials: GJ
authors.lastname: Wang
authors.forename: J S
authors.initials: JS
authors.lastname: Fowler
authors.forename: D
authors.initials: D
authors.lastname: Franceschi
authors.forename: P K
authors.initials: PK
authors.lastname: Thanos
authors.forename: C
authors.initials: C
authors.lastname: Wong
authors.forename: S J
authors.initials: SJ
authors.lastname: Gatley
authors.forename: Y S
authors.initials: YS
authors.lastname: Ding
authors.forename: P
authors.initials: P
authors.lastname: Molina
authors.forename: D
authors.initials: D
authors.lastname: Schlyer
authors.forename: D
authors.initials: D
authors.lastname: Alexoff
authors.forename: R
authors.initials: R
authors.lastname: Hitzemann
authors.forename: N
authors.initials: N
authors.lastname: Pappas
mesh_terms: D000328:Adult; D000435:Alcoholic Intoxication / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008032:Limbic System / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D014055:Tomography, Emission-Computed
chemical_list: D019788:Fluorodeoxyglucose F18; D005947:Glucose