ArticleScientific reports2017
Activation of D1R/PKA/mTOR signaling cascade in medial prefrontal cortex underlying the antidepressant effects of l-SPD.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- The protein interaction networks of mucolipins and two-pore channels.Biochimica et biophysica acta. Molecular cell research · 2019Pooled it
- Acupuncture improves depressive-like behaviors in CUMS rats by modulating lateral habenula synaptic plasticity via the BDNF/ERK/mTOR pathway.Molecular brain · 2025Article
- The Potential Role of Dopamine Pathways in the Pathophysiology of Depression: Current Advances and Future Aspects.CNS & neurological disorders drug targets · 2025Review
- Levo-Stepholidine as a Potential Cognitive Enhancer: Insights into Executive Function and Memory Improvements.Biomedicines · 2024Article
- D1R-5-HT2AR Uncoupling Reduces Depressive Behaviours via HDAC Signalling.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- The pharmacological mechanism of chaihu-jia-longgu-muli-tang for treating depression: integrated meta-analysis and network pharmacology analysis.Frontiers in pharmacology · 2023Article
- Noise Induced Depression-Like Behavior, Neuroinflammation and Synaptic Plasticity Impairments: The Protective Effects of Luteolin.Neurochemical research · 2022Article
- Antidepressant-like effects of cinnamamide derivative M2 via DActa pharmacologica Sinica · 2022Article
- Dopamine Receptors: Is It Possible to Become a Therapeutic Target for Depression?Frontiers in pharmacology · 2022Review
- Proteome Analysis of PC12 Cells Reveals Alterations in Translation Regulation and Actin Signaling Induced by Clozapine.Neurochemical research · 2021Article
- Risky decision-making following prefrontal D1 receptor manipulation.Translational neuroscience · 2021Article
- (-)-Stepholidine blocks expression, but not development, of cocaine conditioned place preference in rats.Neuroscience letters · 2020Article
- Protein Translation and Psychiatric Disorders.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2020Review
- Potential link between the RagA-mTOR-p70S6K axis and depressive-behaviors during bacterial liposaccharide challenge.Journal of neuroinflammation · 2019Article
- Neuromodulators and Long-Term Synaptic Plasticity in Learning and Memory: A Steered-Glutamatergic Perspective.Brain sciences · 2019Review
- The signaling proteins GPR158 and RGS7 modulate excitability of L2/3 pyramidal neurons and control A-type potassium channel in the prelimbic cortex.The Journal of biological chemistry · 2019Article
- Inclusion of enclosed hydration effects in the binding free energy estimation of dopamine D3 receptor complexes.PloS one · 2019Article
- miR-503 suppresses the proliferation and metastasis of esophageal squamous cell carcinoma by triggering autophagy via PKA/mTOR signaling.International journal of oncology · 2018Article
- Mechanisms and Therapeutic Targets of Depression After Intracerebral Hemorrhage.Frontiers in psychiatry · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Major depressive disorder (MDD) is a common neuropsychiatric disorder characterized by diverse symptoms. Although several antidepressants can influence dopamine system in the medial prefrontal cortex (mPFC), but the role of D1R or D2R subtypes of dopamine receptor during anti-depression process is still vague in PFC region. To address this question, we investigate the antidepressant effect of levo-stepholidine (l-SPD), an antipsychotic medication with unique pharmacological profile of D1R agonism and D2R antagonism, and clarified its molecular mechanisms in the mPFC. Our results showed that l-SPD exerted antidepressant-like effects on the Sprague-Dawley rat CMS model of depression. Mechanism studies revealed that l-SPD worked as a specific D1R agonist, rather than D2 antagonist, to activate downstream signaling of PKA/mTOR pathway, which resulted in increasing synaptogenesis-related proteins, such as PSD 95 and synapsin I. In addition, l-SPD triggered long-term synaptic potentiation (LTP) in the mPFC, which was blocked by the inhibition of D1R, PKA, and mTOR, supporting that selective activation of D1R enhanced excitatory synaptic transduction in PFC. Our findings suggest a critical role of D1R/PKA/mTOR signaling cascade in the mPFC during the l-SPD mediated antidepressant process, which may also provide new insights into the role of mesocortical dopaminergic system in antidepressant effects.
Indexed as
Identifiers
What OpenQuestion holds
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.