Pathological circuit function underlying addiction and anxiety disorders
Open accessAbstract
Current models of addiction and anxiety stem from the idea that aberrant function and remodeling of neural circuits cause the pathological behaviors. According to this hypothesis, a disease-defining experience (for example, drug reward or stress) would trigger specific forms of synaptic plasticity, which in susceptible subjects would become persistent and lead to the disease. While the notion of synaptic diseases has received much attention, no candidate disorder has been sufficiently investigated to yield new, rational therapies that could be tested in the clinic. Here we review the arguments in favor of abnormal neuronal plasticity underlying addiction and anxiety disorders, with a focus on the functional diversity of neurons that make up the circuits involved. We argue that future research must strive to obtain a comprehensive description of the relevant functional anatomy. This will allow identification of molecular mechanisms that govern the induction and expression of disease-relevant plasticity in identified neurons. To establish causality, one will have to test whether normalization of function can reverse pathological behavior. With these elements in hand, it will be possible to propose blueprints for manipulations to be tested in translational studies. The challenge is daunting, but new techniques, above all optogenetics, may enable decisive advances.
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The amygdala exhibits profound functional changes as a result of chronic stress that are closely linked to attendant changes in anxiety.
“Moreover, the amygdala exhibits profound functional changes as a result of chronic stress that are closely linked to attendant changes in anxiety (5,6,9–12).”
From Chronic Stress Remodels Synapses in an Amygdala Circuit-Specific Manner (2019) · cites this paper as [5]
Heightened activity within the amygdala is implicated in stress-related emotional abnormalities in humans and animal models.
“Heightened activity within the amygdala, a brain region essential for the regulation of fear and anxiety, has been implicated in stress-related emotional abnormalities in humans and animal models (5–8).”
From Chronic Stress Remodels Synapses in an Amygdala Circuit-Specific Manner (2019) · cites this paper as [5]
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- Authors
- Lüthi, A., & Lüscher, C.
- Affiliations
- Friedrich Miescher Institute (CH)
- University of Geneva (CH)
- Corresponding author
- Lüthi, Andreas
- Lüscher, Christian
- Venue
- Nature Neuroscience
- Published
- 2014-11-17
- Volume
- 17
- Issue
- 12
- Pages
- 1635-1643
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2039953940
- Cited by
- 192
- References
- 100
- Citations by year
- 2026: 2 · 2025: 12 · 2024: 14 · 2023: 13 · 2022: 9 · 2021: 20 · 2020: 9 · 2019: 19 · 2018: 16 · 2017: 17 · 2016: 36 · 2015: 24 · 2014: 1
- FWCI
- 2.97
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (acceptedVersion, other-oa)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- addiction, anxiety disorders, fear circuitry, reward systems, neural circuit dysfunction, synaptic plasticity, neuroplasticity, drug reward, stress, optogenetics
- MeSH terms
- Animals, Anxiety Disorders, Brain, Humans, Neuronal Plasticity, Behavior, Addictive
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