ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2018
Interaction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 74 citations in OpenAlex.
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- Exendin-4 enhances GLP-1 signaling and reduces anxiety-like behaviors in male heroin withdrawal mice.PloS one · 2026Article
- Promising Antidepressant Potential: The Role of Lactobacillus rhamnosus GG in Mental Health and Stress Response.Probiotics and antimicrobial proteins · 2025Article
- Noradrenergic inputs to the basolateral amygdala have bidirectional effects on coping behavior and neuronal activity in mice.bioRxiv : the preprint server for biology · 2025Article
- Phase synchrony between prefrontal noradrenergic and cholinergic signals indexes inhibitory control.Nature communications · 2025Article
- Acute Effects of Four Major Trace Amines on Zebrafish Behavioral, Neurochemical, and Neuroendocrine Responses.Journal of neurochemistry · 2025Article
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- Cafeteria Diet Abstinence Induces Depressive Behavior and Disrupts Endocannabinoid Signaling in Dopaminergic Areas: A Preclinical Study.Current neuropharmacology · 2025Article
- Medial prefrontal cortex acetylcholine signaling mediates the ability to learn an active avoidance response following learned helplessness training.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- The role of the adrenalectomy in the management of pheochromocytoma: the experience of a Portuguese referral center.Endocrine · 2024Article
- Distinct cholinergic circuits underlie discrete effects of reward on attention.Frontiers in molecular neuroscience · 2024Review
- Scientific rationale for the use of α2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders.Molecular psychiatry · 2023Review
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- How can I measure brain acetylcholine levels in vivo? Advantages and caveats of commonly used approaches.Journal of neurochemistry · 2023Review
- Practical considerations when providing palliative care to patients with neuroendocrine tumors in the context of routine disease management or hospice care.Endocrine-related cancer · 2023Review
- Differential Regulation of Prelimbic and Thalamic Transmission to the Basolateral Amygdala by Acetylcholine Receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- ACh signaling modulates activity of the GABAergic signaling network in the basolateral amygdala and behavior in stress-relevant paradigms.Molecular psychiatry · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Medications that target the noradrenergic system are important therapeutics for depression and anxiety disorders. More recently, clinical studies have shown that the α2-noradrenergic receptor (α2AR) agonist guanfacine can decrease stress-induced smoking relapse during acute abstinence, suggesting that targeting the noradrenergic system may aid in smoking cessation through effects on stress pathways in the brain. Acetylcholine (ACh), like the nicotine in tobacco, acts at nicotinic acetylcholine receptors (nAChRs) to regulate behaviors related to anxiety and depression. We therefore investigated interactions between guanfacine and ACh signaling in tests of anxiolytic and antidepressant efficacy in female and male C57BL/6J mice, focusing on the amygdala as a potential site of noradrenergic/cholinergic interaction. The antidepressant-like effects of guanfacine were blocked by shRNA-mediated knockdown of α2AR in amygdala. Knockdown of the high-affinity β2 nAChR subunit in amygdala also prevented antidepressant-like effects of guanfacine, suggesting that these behavioral effects require ACh signaling through β2-containing nAChRs in this brain area. Ablation of NE terminals prevented the anxiolytic- and antidepressant-like effects of the nicotinic partial agonist cytisine, whereas administration of the cholinesterase antagonist physostigmine induced a depression-like phenotype that was not altered by knocking down α2AR in the amygdala. These studies suggest that ACh and NE have opposing actions on behaviors related to anxiety and depression and that cholinergic signaling through β2-containing nAChRs and noradrenergic signaling through α2a receptors in neurons of the amygdala are critical for regulation of these behaviors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.