Examining SLV-323, a novel NK1 receptor antagonist, in a chronic psychosocial stress model for depression
Abstract
Rationale Substance P antagonists have been proposed as candidates for a new class of antidepressant compounds.Objectives We examined the effects of SLV-323, a novel neurokinin 1 receptor (NK1R) antagonist, in the chronic psychosocial stress paradigm of adult male tree shrews.Methods Animals were subjected to a 7 day period of psychosocial stress before being treated daily with SLV-323 (20 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. Norepinephrine excretion was monitored from daily urine samples, and serum testosterone concentrations were measured at the end of the experiment. All animals were videotaped daily to analyze scent-marking behavior and locomotor activity. Cell proliferation in the dentate gyrus and hippocampal volume were measured postmortem.Results Stress significantly decreased cerebral concentrations of N-acetyl-aspartate, total creatine, and choline-containing compounds in vivo and resulted in an increase of urinary norepinephrine and decrease of serum testosterone concentrations. Moreover, stressed animals displayed decreased scent-marking behavior and locomotor activity. The proliferation rate of the granule precursor cells in the dentate gyrus was reduced, and hippocampal volume was mildly decreased. The stress-induced alterations in the central nervous system were partially prevented by concomitant administration of SLV-323, while drug treatment had only a minor effect on the stress-induced behavioral changes.Conclusions The novel NK1R antagonist SLV-323 has certain antidepressant-like effects in a valid animal model of depression.
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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 [99]
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- Authors
- Czéh, B., Pudovkina, O., van der Hart, M. G. C., Simon, M., Heilbronner, U., Michaelis, T., Watanabe, T., Frahm, J., & Fuchs, E.
- Affiliations
- German Primate Center (DE)
- Solvay (Netherlands) (NL)
- Max Planck Society (DE)
- Corresponding author
- Czéh, Boldizsár
- Venue
- Psychopharmacology
- Published
- 2005-02-22
- Volume
- 180
- Issue
- 3
- Pages
- 548-557
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2121198748
- Cited by
- 33
- References
- 56
- Citations by year
- 2024: 1 · 2021: 1 · 2019: 1 · 2017: 1 · 2016: 4 · 2015: 5 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- NK1 receptor antagonists, substance P antagonist, depression, chronic psychosocial stress, tree shrew, antidepressant effects, N-acetylaspartate, creatine, choline-containing compounds, urinary norepinephrine, testosterone, locomotor activity, hippocampal volume, brain metabolites
- MeSH terms
- Animals, Behavior, Animal, Depression, Hippocampus, Male, Motor Activity, Norepinephrine, Magnetic Resonance Spectroscopy, Stress, Psychological, Testosterone, Time Factors, Tupaiidae, Receptors, Neurokinin-1, Dentate Gyrus, Models, Animal, Cell Proliferation, Neurokinin-1 Receptor Antagonists
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