title: Dose-dependent decrease of activation in bilateral amygdala and insula by lorazepam during emotion processing.
abstract: BACKGROUND
  Functional neuroimaging may elucidate the pathophysiologic features of anxiety disorders and the site of action of anxiolytic drugs. A large body of evidence suggests that the amygdala and associated limbic structures play a critical role in the expression of anxiety and may be treatment targets for anxiolytic drugs.
  
  
  OBJECTIVE
  To determine whether lorazepam dose-dependently attenuates blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) activation in the amygdala and associated limbic structures during an emotion face assessment task.
  
  
  METHODS
  Fifteen healthy volunteers participated in a double-blind, placebo-controlled, randomized dose-response study. Subjects underwent imaging 3 times (at least a week apart) and were given either a single-dose placebo or 0.25 mg or 1.0 mg of lorazepam 1 hour prior to an MRI session. During fMRI, subjects completed an emotion face assessment task, which has been shown to elicit amygdala activation.
  
  
  METHODS
  The BOLD-fMRI activation in amygdala, insula, and medial prefrontal cortex during the emotion face assessment task.
  
  
  RESULTS
  Lorazepam significantly attenuated the BOLD-fMRI signal in a dose-dependent manner in bilateral amygdala and insula but not in the medial prefrontal cortex. Lorazepam did not affect the BOLD-fMRI signal in the primary visual cortex.
  
  
  CONCLUSIONS
  The current finding provides the first neuroimaging evidence of a dose-dependent change induced by an established therapeutic agent in brain regions known to be critical for the mediation of anxiety. This investigation may help to support the use of BOLD-fMRI with pharmacological probes to investigate the neural circuits underlying anxiety and the use of fMRI as a tool in the development of new anxiolytic agents.
authors.affiliation: Laboratory of Biological Dynamics and Theoretical Medicine and Department of Psychiatry, University of California, San Diego, USA.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Paulus
authors.forename: Justin S
authors.initials: JS
authors.lastname: Feinstein
authors.forename: Gabriel
authors.initials: G
authors.lastname: Castillo
authors.forename: Alan N
authors.initials: AN
authors.lastname: Simmons
authors.forename: Murray B
authors.initials: MB
authors.lastname: Stein
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001008:Anxiety Disorders / Q000188:drug therapy / Q000523:psychology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004644:Emotions / Q000187:drug effects / Q000502:physiology*; D005149:Facial Expression; D005260:Female; D007839:Functional Laterality / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008140:Lorazepam / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000706:statistics & numerical data; D008297:Male; D010100:Oxygen / Q000097:blood; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology*
chemical_list: D014151:Anti-Anxiety Agents; D008140:Lorazepam; D010100:Oxygen