Cited by 158Neuropeptides and Animal PhysiologyStress Responses and CortisolTreatment of Major Depression

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Substance P receptor antagonist and clomipramine prevent stress-induced alterations in cerebral metabolites, cytogenesis in the dentate gyrus and hippocampal volume

van der Hart, M G C, Czéh, B, de Biurrun, G, Michaelis, T, Watanabe, T, Natt, O, Frahm, J, Fuchs, E·2002·Molecular Psychiatry

DOI 10.1038/sj.mp.4001130

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Abstract

The neuropeptide substance P and its receptor, the neurokinin 1 receptor (NK(1)R) have been proposed as possible targets for new antidepressant therapies. The present study investigated the effect of the NK(1)R antagonist L-760,735 and the tricyclic antidepressant clomipramine in the chronic psychosocial stress paradigm of adult male tree shrews. Animals were subjected to a 7-day period of psychosocial stress before the onset of daily oral administration of L-760,735 (10 mg kg(-1) day(-1)) or clomipramine (50 mg kg(-1) day(-1)). The psychosocial stress continued throughout the treatment period of 28 days. Brain metabolite concentrations were determined in vivo by proton magnetic resonance spectroscopy. Cell proliferation in the dentate gyrus and hippocampal volume were measured post mortem. Stress significantly decreased in vivo concentrations of N-acetyl-aspartate (-14%), creatine and phosphocreatine (-15%) and choline-containing compounds (-15%). The proliferation rate of the granule precursor cells in the dentate gyrus was reduced (-45%), and hippocampal volume was decreased (-14%). The stress-induced changes of brain metabolites, hippocampal volume and dentate cytogenesis rate were prevented by concomitant drug administration. Elevated myo-inositol concentrations after both treatments hint to an astrocytic enhancement. These results suggest that-despite a different pharmacological profile-the NK(1)R antagonist L-760,735, a member of a novel class of antidepressant drugs, has comparable neurobiological efficacy to tricyclic antidepressants such as clomipramine.

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Authors: van der Hart, M. G. C., Czéh, B., de Biurrun, G., Michaelis, T., Watanabe, T., Natt, O., Frahm, J., & Fuchs, E.
Affiliations: German Primate Center (DE)
Max Planck Society (DE)
Corresponding author: Fuchs, E
ORCID: Czéh, B
Watanabe, T
Frahm, J
Venue: Molecular Psychiatry
Publisher: Springer Science and Business Media LLC
Published: 2002-10-01
Volume: 7
Issue: 9
Pages: 933-941
ISSN: 1359-4184 (ISSN-L)
1476-5578
DOI: 10.1038/sj.mp.4001130
OpenAlex: W2065495488
Cited by: 158
References: 61
Citations by year: 2025: 1 · 2024: 4 · 2023: 1 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 2 · 2016: 6 · 2015: 7 · 2014: 3 · 2013: 4 · 2012: 10
FWCI: 5.35
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Molecular Psychiatry (publishedVersion)
PubMed (publishedVersion)
Max Planck Institute for Plasma Physics (submittedVersion)
MPG.PuRe (Max Planck Society) (submittedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords: substance P, neurokinin-1 receptor, clomipramine, chronic psychosocial stress, antidepressants, brain metabolites, N-acetylaspartate, creatine, phosphocreatine, choline-containing compounds, myo-inositol, dentate gyrus, hippocampal volume, granule cell proliferation, astrocytes, tree shrew
MeSH terms: Animals, Antidepressive Agents, Tricyclic, Body Weight, Brain Chemistry, Cell Division, Chronic Disease, Clomipramine, Major Depressive Disorder, Disease Models, Animal, Male, Magnetic Resonance Spectroscopy, Stress, Psychological, Tupaiidae, Dentate Gyrus, Neurokinin-1 Receptor Antagonists

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Substance P receptor antagonist and clomipramine prevent stress-induced alterations in cerebral metabolites, cytogenesis in the dentate gyrus and hippocampal volume

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