The anxious amygdala: CREB signaling and predisposition to anxiety and alcoholism
Open accessAbstract
The amygdala is believed to play a key role in assigning emotional significance to specific sensory input, and conditions such as anxiety, autism, stress, and phobias are thought to be linked to its abnormal function. Growing evidence has also implicated the amygdala in mediation of the stress-dampening properties of alcohol. In this issue of the JCI, Pandey and colleagues identify a central amygdaloid signaling pathway involved in anxiety-like and alcohol-drinking behaviors in rats. They report that decreased phosphorylation of cAMP responsive element-binding protein (CREB) resulted in decreased neuropeptide Y (NPY) expression in the central amygdala of alcohol-preferring rats, causing high anxiety-like behavior. Alcohol intake by these animals was shown to increase PKA-dependent CREB phosphorylation and thereby NPY expression, subsequently ameliorating anxiety-like behavior. These provocative data suggest that a CREB-dependent neuromechanism underlies high anxiety-like and excessive alcohol-drinking behavior.
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Disturbances of the stress axis have long been recognized to occur among patients who are addicts.
“Furthermore, downregulation of striatal dopamine D2 receptor protein expression, observable by raclopride PET [12] and disturbances of the stress axis [13,14], have long been recognized to occur among patients who are addicts, but have not been incorporated into clinical practice, or used in clinical research in any systematic way.”
From Addiction Biomarkers: Dimensional Approaches to Understanding Addiction (2018) · cites this paper as [14]
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References 33 · Cited by 66
- Authors
- Wand, G.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Wand, G.
- ORCID
- Wand, G.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-10-01
- Volume
- 115
- Issue
- 10
- Pages
- 2697-2699
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1236699
- OpenAlex
- W2100630953
- Cited by
- 66
- References
- 33
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 6 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 1 · 2013: 2 · 2012: 2
- FWCI
- 0.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- amygdala, CREB phosphorylation, anxiety-like behavior, alcoholism, neuropeptide Y, central amygdala, protein kinase A, alcohol consumption, stress buffering, alcohol-preferring rats
- MeSH terms
- Alcoholism, Amygdala, Animals, Anxiety, Humans, Neuropeptide Y, Signal Transduction, Cyclic AMP Response Element-Binding Protein, Genetic Predisposition to Disease, Alcohol-Induced Disorders, Nervous System, Rats
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