M2-AChR Mediates Rapid Antidepressant Effects of Scopolamine Through Activating the mTorc1-BDNF Signaling Pathway in the Medial Prefrontal Cortex
Bibliographic Data
| ID | 15523937 |
|---|---|
| Authors | Shuang Liu (0000-0002-8749-3607, Beijing Anding Hospital), Dandan Shi (0000-0003-0856-5105, Capital Medical University), Zuoli Sun (0000-0003-1062-2009, Beijing Anding Hospital), Yi He (0000-0002-5562-4190, Beijing Anding Hospital), Jian Yang (0000-0003-2001-2474, Beijing Anding Hospital, corresponding author), Gang Wang (0000-0002-2288-3807, Beijing Anding Hospital, corresponding author) |
| Year | 2021 |
| Volume | 12 |
| Pages | 601985-601985 |
| Publication date | 2021-05-17 |
| Open Access | Yes |
| Type | ARTICLE |
| Venue | Frontiers in Psychiatry (JOURNAL) |
| Journal identifiers | ISSN: 1664-0640 • E-ISSN: 1664-0640 |
| Publisher | Frontiers Media (PUBLISHER • CH) |
| DOI | 10.3389/fpsyt.2021.601985 |
| PMID | 34093254 |
| OpenAlex | W3160080877 |
| Language | EN |
| References cited | 2 |
Background: Scopolamine, a non-selective muscarinic acetylcholine receptor (M1~5-AChR) antagonist, has rapid and robust antidepressant effects in humans and other species. However, which of the five M-AChRs mediates these therapeutic effects has not been fully identified. Several studies implicate M2-AChR as a potential antidepressant target of scopolamine. This study aimed to explore the role of M2-AChR in scopolamine's antidepressant-like effects and determine the underlying mechanisms. Methods: We used the classic novelty suppressed feeding test (NSFT), open field test (OFT) and forced swim test (FST) to observe antidepressant-related behaviors of normal rats, medial prefrontal cortex (mPFC) neuron silenced rats and M2-AChR knockdown rats treated with scopolamine. In a further experiment, the M2 cholinergic receptor antagonist methoctramine (MCT) was injected intracerebroventricularly into normal rats. Levels of mTORC1 and brain-derived neurotrophic factor (BDNF) in the mPFC of animals were analyzed by Western blotting. Results: Consistent with previous studies, mPFC was required for the antidepressant-like effects of scopolamine, and intracerebroventricular injection of MCT into rats could produce similar antidepressant-like effects. Use of AAV-shRNA to knock down M2-AChR in the mPFC resulted in the antidepressant-like effects of scopolamine being blunted. Furthermore, Western blotting demonstrated increased expression of mTORC1 signaling and BDNF in MCT-treated rats. Conclusion: Our results indicate that M2-AChR in the mPFC mediates the antidepressant-like effects of scopolamine by increasing the expression of BDNF and activating the mTORC1 signaling pathway
Acetylcholine · Antagonist · Antidepressant · Behavioural despair test · Cholinergic · Hippocampus · Methoctramine · mTORC1 · Muscarinic acetylcholine receptor · Muscarinic acetylcholine receptor M1 · Neurotrophic factors · PI3K/AKT/mTOR pathway · Prefrontal cortex · Receptor · Signal transduction · Tail suspension test · Chemistry · Medicine · Neuroscience · Neuroscience and Neuropharmacology Research · Psychology · Receptor Mechanisms and Signaling · Treatment of Major Depression · Endocrinology · Internal Medicine · Pharmacology
| Highly cited | No |
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