ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
5-HT2C receptor agonist anorectic efficacy potentiated by 5-HT1B receptor agonist coapplication: an effect mediated via increased proportion of pro-opiomelanocortin neurons activated.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
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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
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Centrally-acting opioid receptor antagonists as a treatment for antipsychotic-induced weight gain: A systematic review and meta-analysis of clinical trial data.Journal of psychopharmacology (Oxford, England) · 2025Pooled it
- Lorcaserin treatment decreases body weight and reduces cardiometabolic risk factors in obese adults: A six-month, randomized, placebo-controlled, double-blind clinical trial.Diabetes, obesity & metabolism · 2019Trial
- Lac-Phe induces hypophagia by inhibiting AgRP neurons in mice.Nature metabolism · 2025Article
- G proteins of the GScience advances · 2025Article
- Therapeutic Strategies Against Metabolic Imbalance in a Male Mouse Model With 5-HT2CR Loss-of-Function.Endocrinology · 2024Article
- Dysfunction of the adhesion G protein-coupled receptor latrophilin 1 (ADGRL1/LPHN1) increases the risk of obesity.Signal transduction and targeted therapy · 2024Article
- Maternal High Fat Diet in Lactation Impacts Hypothalamic Neurogenesis and Neurotrophic Development, Leading to Later Life Susceptibility to Obesity in Male but Not Female Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Unraveling the serotonin saga: from discovery to weight regulation and beyond - a comprehensive scientific review.Cell & bioscience · 2023Review
- The Serotonergic System and Amyotrophic Lateral Sclerosis: A Review of Current Evidence.Cellular and molecular neurobiology · 2023Review
- 5-HTNutrients · 2023Review
- Unraveling the periprandial changes in brain serotonergic activity and its correlation with food intake-related neuropeptides in rainbow troutFrontiers in endocrinology · 2023Article
- Delineating a serotonin 1B receptor circuit for appetite suppression in mice.The Journal of experimental medicine · 2022Article
- 5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding.Molecular psychiatry · 2021Article
- Role of serotonin in body weight, insulin secretion and glycaemic control.Journal of neuroendocrinology · 2021Review
- Central 5-HTR2C in the Control of Metabolic Homeostasis.Frontiers in endocrinology · 2021Review
- Hypothalamic Pomc expression restricted to GABAergic neurons suppresses Npy overexpression and restores food intake in obese mice.Molecular metabolism · 2020Article
- Nucleus of the Solitary Tract Serotonin 5-HTCell metabolism · 2018Article
- The Leptin, Dopamine and Serotonin Receptors in Hypothalamic POMC-Neurons of Normal and Obese Rodents.Neurochemical research · 2018Article
- Lorcaserin improves glycemic control via a melanocortin neurocircuit.Molecular metabolism · 2017Article
- Activation of Ventral Tegmental Area 5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
An essential component of the neural network regulating ingestive behavior is the brain 5-hydroxytryptamine2C receptor (5-HT2CR), agonists of which suppress food intake and were recently approved for obesity treatment by the US Food and Drug Administration. 5-HT2CR-regulated appetite is mediated primarily through activation of hypothalamic arcuate nucleus (ARC) pro-opiomelanocortin (POMC) neurons, which are also disinhibited through a 5-HT1BR-mediated suppression of local inhibitory inputs. Here we investigated whether 5-HT2CR agonist anorectic potency could be significantly enhanced by coadministration of a 5-HT1BR agonist and whether this was associated with augmented POMC neuron activation on the population and/or single-cell level. The combined administration of subanorectic concentrations of 5-HT2CR and 5-HT1BR agonists produced a 45% reduction in food intake and significantly greater in vivo ARC neuron activation in mice. The chemical phenotype of activated ARC neurons was assessed by monitoring agonist-induced cellular activity via calcium imaging in mouse POMC-EGFP brain slices, which revealed that combined agonists activated significantly more POMC neurons (46%) compared with either drug alone (∼25% each). Single-cell electrophysiological analysis demonstrated that 5-HT2CR/5-HT1BR agonist coadministration did not significantly potentiate the firing frequency of individual ARC POMC-EGFP cells compared with agonists alone. These data indicate a functional heterogeneity of ARC POMC neurons by revealing distinct subpopulations of POMC cells activated by 5-HT2CRs and disinhibited by 5-HT1BRs. Therefore, coadministration of a 5-HT1BR agonist potentiates the anorectic efficacy of 5-HT2CR compounds by increasing the number, but not the magnitude, of activated ARC POMC neurons and is of therapeutic relevance to obesity treatment.
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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.