ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2023
D1R-5-HT2AR Uncoupling Reduces Depressive Behaviours via HDAC Signalling.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 10 citations in OpenAlex.
- Erythropoietin (EPO) Alleviates Chronic Stress-Induced Depression by Modulating SIRT1-Mediated Mitochondrial Function.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Bmal1 haploinsufficiency impairs fear memory and modulates neuroinflammation via the 5-HT2C receptor.Frontiers in pharmacology · 2024Article
- Article
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Dopamine and serotonin signalling are associated with major depressive disorder, which is a prevalent life-threatening illness worldwide. Numerous FDA-approved dopamine/serotonin signalling-modifying drugs are available but are associated with concurrent side effects and limited efficacy. Thus, identifying and targeting their signalling pathway is crucial for improving depression treatment. Here, we determined that serotonin receptor 2A (5-HT2AR) abundantly forms a protein complex with dopamine receptor 1 (D1R) in high abundance via its carboxy-terminus in the brains of mice subjected to various chronic stress paradigms. Furthermore, the D1R/5-HT2AR interaction elicited CREB/ERK/AKT modulation during synaptic regulation. An interfering peptide (TAT-5-HT2AR-SV) agitated the D1R/5-HT2AR interaction and attenuated depressive symptoms accompanied by CREB/ERK molecule costimulation. Interestingly, HDAC antagonism but not TrkB antagonism reversed the antidepressant effect of competitive peptides. These findings revealed a novel D1R/5-HT2AR heteroreceptor complex mechanism in the pathophysiology of depression, and their uncoupling ameliorates depressive-like behaviours through HDAC-, and not BDNF-, dependent mechanisms.
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Registered trials
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