Leicht, Gregor and Mulert, Christoph and Eser, Daniela and Saemann, Philipp G. and Ertl, Matthias and Laenger, Anna and Karch, Susanne and Pogarell, Oliver and Meindl, Thomas and Czisch, Michael and Rupprecht, Rainer (2013) Benzodiazepines Counteract Rostral Anterior Cingulate Cortex Activation Induced by Cholecystokinin-Tetrapeptide in Humans. BIOLOGICAL PSYCHIATRY, 73 (4). pp. 337-344. ISSN 0006-3223, 1873-2402
Full text not available from this repository. (Request a copy)Abstract
Background: Benzodiazepines modulate gamma-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INDEPENDENT COMPONENT ANALYSIS; PREMENSTRUAL DYSPHORIC DISORDER; CCK-4-INDUCED PANIC-ATTACKS; HEALTHY-VOLUNTEERS; FUNCTIONAL NEUROANATOMY; AMYGDALA INTERACTIONS; ANTICIPATORY ANXIETY; CONDITIONED FEAR; RAT-BRAIN; ADULT-RAT; ACC; alprazolam; anxiety; benzodiazepine; CCK-4; fMRI |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Apr 2020 09:54 |
| Last Modified: | 24 Apr 2020 09:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17142 |
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