ArticleNeuropharmacology2020
Examining the role of muscarinic M5 receptors in VTA cholinergic modulation of depressive-like and anxiety-related behaviors in rats.
Article in Neuropharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Clinical Effectiveness of Muscarinic Receptor-Targeted Interventions in Neuropsychiatric Disorders: A Systematic Review.CNS drugs · 2022Pooled it
- Dysregulation of local inhibitory inputs onto laterodorsal tegmental nucleus cholinergic neurons drives depression-like behaviors in mice.Molecular psychiatry · 2026Article
- Negative affective states are not detected in rats following an intravenous self-administration regimen leading to incubation of oxycodone craving.bioRxiv : the preprint server for biology · 2026Article
- Altered acetylcholine modulations and corticoaccumbal pathway in P11-linked social dysfunction.Molecular psychiatry · 2026Article
- Behavioral Phenotyping of WAG/Rij Rat Model of Absence Epilepsy: The Link to Anxiety and Sex Factors.Biomedicines · 2025Article
- Muscarinic Receptor Activation Preferentially Inhibits Rebound in Vulnerable Dopaminergic Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- A golden age of muscarinic acetylcholine receptor modulation in neurological diseases.Nature reviews. Drug discovery · 2024Review
- L-type calcium channel regulation of depression, anxiety and anhedonia-related behavioral phenotypes following chronic stress exposure.Neuropharmacology · 2024Article
- Development of VU6036864: A Triazolopyridine-Based High-Quality Antagonist Tool Compound of the MJournal of medicinal chemistry · 2024Article
- Muscarinic receptor activation preferentially inhibits rebound in vulnerable dopaminergic neurons.bioRxiv : the preprint server for biology · 2024Article
- Targeting the Actions of Muscarinic Receptors on Dopamine Systems: New Strategies for Treating Neuropsychiatric Disorders.Annual review of pharmacology and toxicology · 2024Review
- Ventral Tegmental Area M5 Muscarinic Receptors Mediate Effort-Choice Responding and Nucleus Accumbens Dopamine in a Sex-Specific Manner .The Journal of pharmacology and experimental therapeutics · 2023Article
- Discovery of a potent MBioorganic & medicinal chemistry letters · 2022Article
- Discovery of a potent MBioorganic & medicinal chemistry letters · 2022Article
- Potential of Heterogeneous Compounds as Antidepressants: A Narrative Review.International journal of molecular sciences · 2022Review
- Drug Design Targeting the Muscarinic Receptors and the Implications in Central Nervous System Disorders.Biomedicines · 2022Review
- Identification of a Novel Allosteric Site at the MACS chemical neuroscience · 2021Article
- Targeting muscarinic receptors to treat schizophrenia.Behavioural brain research · 2021Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Acetylcholine is implicated in mood disorders including depression and anxiety. Increased cholinergic tone in humans and rodents produces pro-depressive and anxiogenic-like effects. Cholinergic receptors in the ventral tegmental area (VTA) are known to mediate these responses in male rats, as measured by the sucrose preference test (SPT), elevated plus maze (EPM), and the forced swim test (FST). However, these effects have not been examined in females, and the VTA muscarinic receptor subtype(s) mediating the pro-depressive and anxiogenic-like behavioral effects of increased cholinergic tone are unknown. We first examined the behavioral effects of increased VTA cholinergic tone in male and female rats, and then determined whether VTA muscarinic M5 receptors were mediating these effects. VTA infusion of the acetylcholinesterase inhibitor physostigmine (0.5 μg, 1 μg and 2 μg/side) in males and females produced anhedonic-like, anxiogenic, pro-depressive-like responses on the SPT, EPM, and FST. In females, VTA administration of the muscarinic M5 selective negative allosteric modulator VU6000181 (0.68 ng, 2.3 ng, 6.8 ng/side for a 3 μM, 10 μM, 30 μM/side infusion) did not alter SPT, EPM nor FST behavior. However, in males intra-VTA infusion of VU6000181 alone reduced time spent immobile on the FST. Furthermore, co-infusion of VU6000181 with physostigmine, in male and female rats, attenuated the pro-depressive and anxiogenic-like behavioral responses induced by VTA physostigmine alone, in the SPT, EPM, and FST. Together, these data reveal a critical role of VTA M5 receptors in mediating the anhedonic, anxiogenic, and depressive-like behavioral effects of increased cholinergic tone in the VTA.
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