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Arch Gen Psychiatry. 2005 Mar;62(3):282-8.

Dose-dependent decrease of activation in bilateral amygdala and insula by lorazepam during emotion processing.

Author information

  • 1Laboratory of Biological Dynamics and Theoretical Medicine and Department of Psychiatry, University of California, San Diego, USA.

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.

PARTICIPANTS AND DESIGN:

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.

MAIN OUTCOME MEASURES:

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.

PMID:
15753241
[PubMed - indexed for MEDLINE]
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