Ventral tegmental area muscarinic receptors modulate depression and anxiety-related behaviors in rats
Open accessAbstract
Cholinergic and dopaminergic mechanisms within the mesolimbic dopamine system are suggested to play a role in the manifestation of depression and anxiety-related disorders. However, despite the fact that cholinergic mechanisms in the ventral tegmental area (VTA) highly regulate dopamine activity, the role of VTA cholinergic mechanisms in depression-related behaviors is relatively unknown. Here we sought to determine whether enhancing cholinergic tone in the VTA would alter depression and anxiety-related behavior in the forced swim test (FST), elevated plus maze (EPM) and sucrose preference test (SPT). Adult Sprague Dawley male rats received VTA infusion of the acetylcholinesterase inhibitor, physostigmine (0, 1, 2μg/side), immediately prior to the FST, EPM, or SPT. Physostigmine administration increased immobility time in the FST, decreased time spent on open arms in the EPM, and decreased sucrose preference. We also examined whether activation of VTA muscarinic receptors was sufficient to alter behavior in the FST and EPM. Similar to physostigmine, VTA infusion of the muscarinic receptor agonist, pilocarpine (0, 3, 30μg/side), increased immobility time in the FST and decreased time spent on open arms in the EPM. These data suggest that enhanced VTA cholinergic tone promotes pro-depressive and anxiogenic-like effects and demonstrate that specific activation of VTA muscarinic receptors is also sufficient to induce pro-depressive and anxiogenic responses. Together, these findings reveal a novel role of VTA cholinergic, and specifically muscarinic receptor, mechanisms in mediating responses to stress and anxiety.
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Enhanced ventral tegmental area cholinergic tone increases forced-swim immobility and anhedonia through muscarinic acetylcholine receptors.
“Enhanced VTA cholinergic tone increases forced-swim immobility and anhedonia through mAChRs [45]”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [45]
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- Authors
- Small, K. M., Nunes, E., Hughley, S., & Addy, N. A.
- Affiliations
- Yale University (US)
- Corresponding author
- Addy, Nii A.
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 616
- Pages
- 80-85
- ISSN
- 0304-3940 (ISSN-L)
- PMC
- PMC4798862
- OpenAlex
- W2257827475
- Cited by
- 43
- References
- 45
- Citations by year
- 2025: 5 · 2024: 3 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 2 · 2016: 2
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (R01MH093897, T32MH014276)
- National Institute on Drug Abuse (R21DA038048)
- National Institute of General Medical Sciences (R25GM104553)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- ventral tegmental area, muscarinic receptors, cholinergic tone, depression, anxiety, physostigmine, pilocarpine, acetylcholinesterase inhibition, forced swim test, elevated plus maze, sucrose preference, mesolimbic dopamine system, stress response
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Cholinesterase Inhibitors, Depression, Food Preferences, Male, Motor Activity, Physostigmine, Pilocarpine, Receptors, Muscarinic, Rats, Sprague-Dawley, Ventral Tegmental Area, Muscarinic Agonists, Maze Learning
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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