ArticleThe international journal of neuropsychopharmacology2015
Hippocampal-Dependent Antidepressant Action of the H3 Receptor Antagonist Clobenpropit in a Rat Model of Depression.
Article in The international journal of neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 41 citations in OpenAlex.
- Preclinical Evidence for Antidepressant-like Effects of Histamine H3 Receptor Modulation: A Systematic Review and Meta-Analysis.Life (Basel, Switzerland) · 2026Review
- Two subtypes of major depressive disorder are identified from individualized gray matter morphological abnormalities in a large multi-site dataset.Psychological medicine · 2025Article
- An Updated Bio-Behavioral Profile of the Flinders Sensitive Line Rat: Reviewing the Findings of the Past Decade.Pharmacology research & perspectives · 2025Review
- Targeting Microglia in Neuroinflammation: H3 Receptor Antagonists as a Novel Therapeutic Approach for Alzheimer's Disease, Parkinson's Disease, and Autism Spectrum Disorder.Pharmaceuticals (Basel, Switzerland) · 2024Review
- The major biogenic amine metabolites in mood disorders.Frontiers in psychiatry · 2024Review
- 5HT1AR-FGFR1 Heteroreceptor Complexes Differently Modulate GIRK Currents in the Dorsal Hippocampus and the Dorsal Raphe Serotonin Nucleus of Control Rats and of a Genetic Rat Model of Depression.International journal of molecular sciences · 2023Article
- Potential of Heterogeneous Compounds as Antidepressants: A Narrative Review.International journal of molecular sciences · 2022Review
- The Impact of Chronic Unpredictable Mild Stress-Induced Depression on Spatial, Recognition and Reference Memory Tasks in Mice: Behavioral and Histological Study.Behavioral sciences (Basel, Switzerland) · 2022Article
- Revisiting Preclinical Observations of Several Histamine H3 Receptor Antagonists/Inverse Agonists in Cognitive Impairment, Anxiety, Depression, and Sleep-Wake Cycle Disorder.Frontiers in pharmacology · 2022Review
- Histamine and histamine receptors: Roles in major depressive disorder.Frontiers in psychiatry · 2022Review
- Brain histamine modulates recognition memory: possible implications in major cognitive disorders.British journal of pharmacology · 2020Review
- Are Polyunsaturated Fatty Acids Implicated in Histaminergic Dysregulation in Bipolar Disorder?: AN HYPOTHESIS.Frontiers in physiology · 2018Review
- Histamine Receptors in the Cross-Talk between Periphery and Brain.The international journal of neuropsychopharmacology · 2017Article
- S 38093, a histamine HScientific reports · 2017Article
- Beyond Emotional and Spatial Processes: Cognitive Dysfunction in a Depressive Phenotype Produced by Long Photoperiod Exposure.PloS one · 2017Article
- The Synergistic Enhancing-Memory Effect of Donepezil and S 38093 (a Histamine HFrontiers in pharmacology · 2016Article
- Running Opposes the Effects of Social Isolation on Synaptic Plasticity and Transmission in a Rat Model of Depression.PloS one · 2016Article
- Altered explorative strategies and reactive coping style in the FSL rat model of depression.Frontiers in behavioral neuroscience · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHistamine is a modulatory neurotransmitter regulating neuronal activity. Antidepressant drugs target modulatory neurotransmitters, thus ultimately regulating glutamatergic transmission and plasticity. Histamine H3 receptor (H3R) antagonists have both pro-cognitive and antidepressant effects; however, the mechanism by which they modulate glutamate transmission is not clear. We measured the effects of the H3R antagonist clobenpropit in the Flinders Sensitive Line (FSL), a rat model of depression with impaired memory and altered glutamatergic transmission.
methodsBehavioral tests included the forced swim test, memory tasks (passive avoidance, novel object recognition tests), and anxiety-related paradigms (novelty suppressed feeding, social interaction, light/dark box tests). Hippocampal protein levels were detected by Western blot. Hippocampal plasticity was studied by in slice field recording of CA3-CA1 long-term synaptic potentiation (LTP), and glutamatergic transmission by whole-cell patch clamp recording of excitatory postsynaptic currents (EPSCs) in CA1 pyramidal neurons.
resultsClobenpropit, administered systemically or directly into the hippocampus, decreased immobility during the forced swim test; systemic injections reversed memory deficits and increased hippocampal GluN2A protein levels. FSL rats displayed anxiety-related behaviors not affected by clobenpropit treatment. Clobenpropit enhanced hippocampal plasticity, but did not affect EPSCs. H1R and H2R antagonists prevented the clobenpropit-induced increase in LTP and, injected locally into the hippocampus, blocked clobenpropit's effect in the forced swim test.
conclusionsClobenpropit's antidepressant effects and the enhanced synaptic plasticity require hippocampal H1R and H2R activation, suggesting that clobenpropit acts through disinhibition of histamine release. Clobenpropit reverses memory deficits and increases hippocampal GluN2A expression without modifying anxiety-related phenotypes or EPSCs in CA1 pyramidal neurons.
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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.