ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Serotonin evokes endocannabinoid release and retrogradely suppresses excitatory synapses.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 114 citations in OpenAlex.
- Widespread synaptic density loss in schizophrenia follows molecular and network architecture.Molecular psychiatry · 2026Article
- Serotonin-endocannabinoid crosstalk selectively regulates inhibitory GABAergic inputs in the medial prefrontal cortex.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Filtering the noise: a cerebellar-centered framework for understanding and treating mental illness -a paradigm shift in psychiatry.Frontiers in psychiatry · 2026Article
- 5-HTFrontiers in pharmacology · 2026Article
- Association between lifetime co-use of classic psychedelics and cannabis and prostate cancer diagnosis among US adults 50 years and older.Scientific reports · 2025Article
- The endocannabinoidome-gut microbiome-brain axis as a novel therapeutic target for autism spectrum disorder.Journal of biomedical science · 2025Review
- Cannabinoid overrides triggers of GABAergic plasticity in vestibular circuits and distorts the development of navigation.iScience · 2025Article
- Allosteric Modulators of Serotonin Receptors: A Medicinal Chemistry Survey.Pharmaceuticals (Basel, Switzerland) · 2024Review
- The effects of serotonergic psychedelics in synaptic and intrinsic properties of neurons in layer II/III of the orbitofrontal cortex.Psychopharmacology · 2023Article
- Cortical structural differences following repeated ayahuasca use hold molecular signatures.Frontiers in neuroscience · 2023Article
- Molecular Pathways of the Therapeutic Effects of Ayahuasca, a Botanical Psychedelic and Potential Rapid-Acting Antidepressant.Biomolecules · 2022Review
- Space and Time Coherent Mapping for Subcellular Resolution of Imaging Mass Spectrometry.Cells · 2022Article
- The Impact of Marijuana on Antidepressant Treatment in Adolescents: Clinical and Pharmacologic Considerations.Journal of personalized medicine · 2021Article
- The bidirectional effect of prelimbic 5-hydroxytryptamine type-4 (5-HT4) receptors on ACPA-mediated aversive memory impairment in adult male Sprague-Dawley rats.Iranian journal of basic medical sciences · 2021Article
- Cannabis use, abuse, and withdrawal: Cannabinergic mechanisms, clinical, and preclinical findings.Journal of neurochemistry · 2021Review
- Elevated Brain Fatty Acid Amide Hydrolase Induces Depressive-Like Phenotypes in Rodent Models: A Review.International journal of molecular sciences · 2021Review
- Inflammation induces developmentally regulated sumatriptan inhibition of spinal synaptic transmission.British journal of pharmacology · 2020Article
- Effects of combined 5-HTPsychopharmacology · 2020Article
- The epigenetic legacy of illicit drugs: developmental exposures and late-life phenotypes.Environmental epigenetics · 2019Review
- Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
5-HT(2)-type serotonin receptors (5-HT(2)Rs) are widely expressed throughout the brain and mediate many of the modulatory effects of serotonin. It has been thought that postsynaptic 5-HT(2)Rs act primarily by depolarizing neurons and thereby increasing their excitability. However, it is also known that 5-HT(2)Rs are coupled to G(q/11)-type G-proteins and that some other types of G(q/11)-coupled receptors can regulate synapses by evoking endocannabinoid release and activating presynaptic cannabinoid-type 1 receptors (CB(1)Rs). Here, we examine whether activation of 5-HT(2)Rs can regulate synapses through such a mechanism by studying excitatory synapses onto cells in the inferior olive (IO). These cells express 5-HT(2)Rs on their soma and dendrites, and the IO receives extensive serotonergic input. We find that the excitatory synaptic inputs onto IO cells are strongly suppressed by serotonin receptor agonists as well as release of endogenous serotonin. Both 5-HT(2)Rs and 5-HT(1B)Rs contribute to this modulation by decreasing the probability of glutamate release from presynaptic boutons. The suppression by 5-HT(2)Rs is of particular interest because it is prevented by CB(1)R antagonists, and 5-HT(2)Rs are thought to be located only postsynaptically on IO cells. Our results indicate that serotonin activates 5-HT(2)Rs on IO neurons, thereby releasing endocannabinoids that act retrogradely to suppress glutamate release by activating presynaptic CB(1)Rs. These findings establish a link between serotonin signaling and endocannabinoid signaling. Based on the extensive distribution of 5-HT(2)Rs and CB(1)Rs, it seems likely that this mechanism could mediate many of the actions of 5-HT(2)Rs throughout the brain.
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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.