ArticlePsychopharmacology2013
Acute 5-HT₁A autoreceptor knockdown increases antidepressant responses and serotonin release in stressful conditions.
Article in Psychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 68 citations in OpenAlex.
- The Influence of Acute SSRI Administration on White Matter Microstructure in Patients Suffering From Major Depressive Disorder and Healthy Controls.The international journal of neuropsychopharmacology · 2021Trial
- The C/C Genotype of the C-1019G (rs6295) Polymorphism of the 5-HT1A Receptor Gene Is Associated with Lower Susceptibility to Depressive Symptoms in a Rural Population in Mexico.Neurology international · 2025Article
- Chronic Fluoxetine Treatment Desensitizes Serotoninergic Inhibition of GABAergic Inputs and Intrinsic Excitability of Dorsal Raphe Serotonin Neurons.Brain sciences · 2025Article
- Activating the Astrocytes of the Dorsal Raphe Nucleus via Its Neural Circuits With the Medial Prefrontal Cortex Improves Depression in Mice.Behavioural neurology · 2025Article
- The Implication of 5-HT Receptor Family Members in Aggression, Depression and Suicide: Similarity and Difference.International journal of molecular sciences · 2022Review
- Role of 5-HT1A-mediated upregulation of brain indoleamine 2,3 dioxygenase 1 in the reduced antidepressant and antihyperalgesic effects of fluoxetine during maintenance treatment.Frontiers in pharmacology · 2022Article
- Serotonin 2A receptor function and depression-like behavior in rats model of hypothyroidism.Experimental brain research · 2021Article
- Region- and receptor-specific effects of chronic social stress on the central serotonergic system in mice.IBRO neuroscience reports · 2021Article
- Pivotal mental states.Journal of psychopharmacology (Oxford, England) · 2021Review
- Genetic, epigenetic and posttranscriptional mechanisms for treatment of major depression: the 5-HT1A receptor gene as a paradigmJournal of psychiatry & neuroscience : JPN · 2019Review
- Selective Knockdown of TASK3 Potassium Channel in Monoamine Neurons: a New Therapeutic Approach for Depression.Molecular neurobiology · 2019Article
- Effects of 5HT1A Activation on Depression Profile Following 5-HT Depletion in Rats Lacking Social Attachment Since Weanling.Psychiatry investigation · 2018Article
- Receptor⁻Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment.Molecules (Basel, Switzerland) · 2018Review
- Emotional Roles of Mono-Aminergic Neurotransmitters in Major Depressive Disorder and Anxiety Disorders.Frontiers in psychology · 2018Review
- Serotonin and brain function: a tale of two receptors.Journal of psychopharmacology (Oxford, England) · 2017Review
- Blunted 5-HTPsychopharmacology · 2017Article
- Therapeutic Potential of Conjugated siRNAs for the Treatment of Major Depressive Disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- A Lack of Serotonin 1B Autoreceptors Results in Decreased Anxiety and Depression-Related Behaviors.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Development of a mechanism-based pharmacokinetic/pharmacodynamic model to characterize the thermoregulatory effects of serotonergic drugs in mice.Acta pharmaceutica Sinica. B · 2016Article
- 5-HT 1A Agonist Properties Contribute to a Robust Response to Vilazodone in the Novelty Suppressed Feeding Paradigm.The international journal of neuropsychopharmacology · 2016Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
rationaleIdentifying the etiological factors in anxiety and depression is critical to develop more efficacious therapies. The inhibitory serotonin(1A) receptors (5-HT(1A)R) located on 5-HT neurons (autoreceptors) limit antidepressant responses and their expression may be increased in treatment-resistant depressed patients.
objectivesRecently, we reported that intranasal administration of modified small interference RNA (siRNA) molecules targeting 5-HT(1A)R in serotonergic neurons evoked antidepressant-like effects. Here we extended this finding using marketed siRNAs against 5-HT(1A)R (1A-siRNA) to reduce directly the 5-HT(1A) autoreceptor expression and evaluate its biological consequences under basal conditions and in response to stressful situations.
methodsAdult mice were locally infused with vehicle, nonsense siRNA, and 1A-siRNA into dorsal raphe nucleus (DR). 5-HT(1A)R knockout mice (1A-KO) were also used. Histological approaches, in vivo microdialysis, and stress-related behaviors were performed to assess the effects of 5-HT(1A) autoreceptor knockdown.
resultsIntra-DR 1A-siRNA infusion selectively reduced 5-HT(1A)R mRNA and binding levels and canceled 8-OH-DPAT-induced hypothermia. Basal extracellular 5-HT in medial prefrontal cortex (mPFC) did not differ among treatments. However, 1A-siRNA-treated mice displayed less immobility in the tail suspension and forced swim tests, as did 1A-KO mice. This was accompanied by a greater increase in prefrontal 5-HT release during tail suspension test. Moreover, intra-DR 1A-siRNA infusion augmented the increase of extracellular 5-HT in mPFC evoked by fluoxetine, up to the level in 1A-KO mice.
conclusionTogether with our previous report, the present results indicate that acute suppression of 5-HT(1A) autoreceptor expression evokes robust antidepressant-like effects, likely mediated by an increased capacity of serotonergic neurons to release 5-HT in stressful conditions.
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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.