title: One milligram of lorazepam does not decrease anxiety induced by CCK-4 in healthy volunteers: investigation of neural correlates with BOLD MRI.
abstract: Benzodiazepine effects on cholecystokinin tetrapeptide (CCK-4)-induced panic attack (PA) in humans are incompletely characterized, in particular on the neurofunctional level. This work explores the effects of lorazepam on brain activity and behavioral and physiological symptoms related to CCK-4-induced PA in healthy volunteers. Twenty-one male volunteers received 1 mg of lorazepam or placebo orally, 2 hours before an injection of 0.9% saline solution followed by 50 µg of CCK-4 during functional magnetic resonance imaging (fMRI) and heart rate recording. Panic attacks were defined using the panic symptom scale (PSS). In addition, the Y1-STAI (state anxiety) and the Bond & Lader Visual Analogue Scale (VAS) were used. Eleven subjects were classified as panickers. CCK-4 induced behavioral anxiety and cardiovascular effects along with cerebral activation in anxiety-related brain regions. Overall, lorazepam did not significantly modify the anxiogenic and cardiovascular effects of CCK-4. Regarding CCK-4-induced brain activation, lorazepam did not reduce activity in the insulae and cingulate gyrus of panickers. One milligram of lorazepam was not sufficient to reverse strong panicogenic effects, but decreased brain activity in the case of mild anxiety.
authors.affiliation: FORENAP, Rouffach, France. therese.schunck@isl.eu
authors.forename: Thérèse
authors.initials: T
authors.lastname: Schunck
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mathis
authors.forename: Gilles
authors.initials: G
authors.lastname: Erb
authors.forename: Izzie Jacques
authors.initials: IJ
authors.lastname: Namer
authors.forename: Yann
authors.initials: Y
authors.lastname: Hode
authors.forename: Agnès
authors.initials: A
authors.lastname: Demazières
authors.forename: Rémy
authors.initials: R
authors.lastname: Luthringer
mesh_terms: D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001007:Anxiety / Q000139:chemically induced* / Q000503:physiopathology*; D001008:Anxiety Disorders / Q000503:physiopathology; D001288:Attention / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D018592:Cross-Over Studies; D006179:Gyrus Cinguli / Q000187:drug effects / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008140:Lorazepam / Q000008:administration & dosage* / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D010200:Panic / Q000187:drug effects* / Q000502:physiology; D016584:Panic Disorder / Q000139:chemically induced / Q000503:physiopathology; D011569:Psychiatric Status Rating Scales; D013758:Tetragastrin / Q000009:adverse effects* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D014151:Anti-Anxiety Agents; D013758:Tetragastrin; D008140:Lorazepam