Benzodiazepines counteract rostral anterior cingulate cortex activation induced by cholecystokinin-tetrapeptide in humans
Abstract
Background Benzodiazepines modulate γ-aminobutyric acid type A (GABA(A)) 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 (r(p) = .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.
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Benzodiazepine administration increases connectivity between the rostral ACC and the amygdala.
“an increased connectivity between the rostral ACC and the amygdala after adminstration of a benzodiazepine (Leicht et al., 2013)”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Leicht et al., 2013
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- Authors
- Leicht, G., Mulert, C., Eser, D., Sämann, P. G., Ertl, M., Laenger, A., Karch, S., Pogarell, O., Meindl, T., Czisch, M., & Rupprecht, R.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Ludwig-Maximilians-Universität München (DE)
- Max Planck Society (DE)
- University of Regensburg (DE)
- Corresponding author
- Leicht, Gregor
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 73
- Issue
- 4
- Pages
- 337-344
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2030108396
- Cited by
- 21
- References
- 60
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2017: 2 · 2016: 5 · 2015: 1 · 2014: 1 · 2013: 3
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- benzodiazepines, alprazolam, rostral anterior cingulate cortex, CCK-4, anxiety, anxiolytic effects, GABAA receptor, amygdala, prefrontal cortex, functional connectivity
- MeSH terms
- Adult, Alprazolam, Anxiety, Brain, Brain Mapping, Double-Blind Method, Gyrus Cinguli, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Tetragastrin, Anti-Anxiety Agents, GABA Modulators
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