title: Functional magnetic resonance imaging of alprazolam-induced changes in humans with familial alcoholism.
abstract: This study sought to identify whether subjects with a family history (FH + ) of alcoholism had changes in regional cerebral blood volume (rCBV) after an alprazolam challenge which distinguished them from subjects without a family history (FH -) of alcoholism using functional MRI (fMRI). Twelve FH + and eight FH - subjects were challenged with 1 mg of alprazolam or placebo in a double-blind crossover design. FMRI scans were obtained at baseline, 1 and 2 h after the challenge using the dynamic susceptibility contrast method with gadolinium. Mood scales, the Tufts Addiction Research Center Inventory-Morphine Benzedrine Group Scale and the drug liking scale, were administered every 30 min to assess drug effects. Global analysis of CBV showed a treatment by time decrease on alprazolam relative to placebo, but no effect by family history. The FH + group showed rCBV decreases at 1 h in the left caudate and left inferior prefrontal region, while the FH - group showed rCBV decreases at 2 h in the right inferior prefrontal region and anterior cingulate in response to alprazolam relative to placebo. FH + subjects reported more mood enhancement with alprazolam. This fMRI technique detected global and regional CBV changes induced by alprazolam. The location and rate of alprazolam-induced rCBV changes differed between FH + and FH - subjects. These changes may be related to the increased mood enhancement found in subjects genetically predisposed to alcoholism.
authors.affiliation: Department of Psychiatry/116A, Outpatient Clinic, Boston National Institute on Drug Abuse/Veterans Administration Medication Development Research Unit, MA 02114, USA. streeter.chris@boston.va.gov
authors.forename: C C
authors.initials: CC
authors.lastname: Streeter
authors.forename: D A
authors.initials: DA
authors.lastname: Ciraulo
authors.forename: G J
authors.initials: GJ
authors.lastname: Harris
authors.forename: M J
authors.initials: MJ
authors.lastname: Kaufman
authors.forename: R F
authors.initials: RF
authors.lastname: Lewis
authors.forename: C M
authors.initials: CM
authors.lastname: Knapp
authors.forename: A M
authors.initials: AM
authors.lastname: Ciraulo
authors.forename: L C
authors.initials: LC
authors.lastname: Maas
authors.forename: M
authors.initials: M
authors.lastname: Ungeheuer
authors.forename: S
authors.initials: S
authors.lastname: Szulewski
authors.forename: P F
authors.initials: PF
authors.lastname: Renshaw
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D000437:Alcoholism / Q000378:metabolism*; D000525:Alprazolam / Q000494:pharmacology*; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D017352:Echo-Planar Imaging; D005260:Female; D007839:Functional Laterality; D006801:Humans; D008297:Male
chemical_list: D014151:Anti-Anxiety Agents; D000525:Alprazolam