Background
Benzodiazepines modulate γ-aminobutyric acid type A (GABAA) receptors throughout the brain. However, it is not fully understood which brain
regions within anxiety-related brain circuits are really responsible for their anxiolytic
effects and how these regions interact.
Methods
We investigated whether the benzodiazepine alprazolam affects activity in distinct
brain regions within anxiety-related circuits during an experimental anxiety paradigm
by means of functional magnetic resonance imaging (fMRI). Panic symptoms were elicited
by a bolus injection of the neuropeptide cholecystokinin-tetrapeptide (CCK-4) in 16
healthy male subjects in a double-blind, placebo-controlled design. Functional brain
activation patterns were determined before and during the CCK-4-challenge without
pretreatment and after treatment with either placebo or 1 mg alprazolam.
Results
The CCK-4 induced anxiety and elicited widely distributed activation patterns in anxiety-related
brain circuits, especially in the rostral anterior cingulate cortex (rACC), which
was attenuated after alprazolam treatment. In contrast to placebo, alprazolam abolished
the activation of the rACC after challenge with CCK-4 (p<.005, corrected for multiple comparisons) and increased functional connectivity between
the rACC and other anxiety-related brain regions such as amygdala and prefrontal cortex.
Moreover, the reduction in the CCK-4 induced activation of the rACC correlated with
the anxiolytic effect of alprazolam (rp = .52; p = .04).
Conclusions
These findings put forward the rACC as a target for benzodiazepines and suggest that
the CCK-4/fMRI paradigm might represent a human translational model for the investigation
of anxiolytic drugs.
Key Words
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Article Info
Publication History
Published online: October 10, 2012
Accepted:
September 4,
2012
Received in revised form:
September 4,
2012
Received:
February 9,
2012
Footnotes
Authors GL and CM contributed equally to this work.
Identification
Copyright
© 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
