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

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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  • NK1R antagonism can mitigate alterations in the brain induced by chronic psychological stress, which is associated with visceral hypersensitivity and spinal NK1R up-regulation in female rodents and possibly in mice with induced endometriosis.

    “Aside from delaying fibrogenesis, NK1R antagonism can also mitigate alterations in the brain induced by chronic psychological stress99–101, which is associated with visceral hypersensitivity and spinal NK1R up-regulation in female rodents102,103 and possibly in mouse with induced endometriosis as well104–106.”

    From Neuropeptides Substance P and Calcitonin Gene Related Peptide Accelerate the Development and Fibrogenesis of Endometriosis (2019) · cites this paper as [101]

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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
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
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 › 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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