Examining SLV-323, a novel NK1 receptor antagonist, in a chronic psychosocial stress model for depression

Boldizsár Czéh, Olga Pudovkina, Marieke G C Van Der Hart, M. Simón, Urs Heilbronner, Thomas Michaelis, Takashi Watanabe, Jens Frahm, Eberhard Fuchs

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)548-557
Number of pages10
JournalPsychopharmacology
Volume180
Issue number3
DOIs
Publication statusPublished - Jul 2005

Fingerprint

Neurokinin-1 Receptor Antagonists
Dentate Gyrus
Locomotion
Depression
Antidepressive Agents
Testosterone
Norepinephrine
Tupaiidae
Creatine
Substance P
Choline
Serum
Central Nervous System
Animal Models
Cell Proliferation
Urine
Brain
Pharmaceutical Preparations

Keywords

  • Antidepressant
  • Behavior
  • Hippocampus
  • Mood disorder
  • Neurogenesis
  • Proton magnetic resonance spectroscopy
  • Substance P
  • Testosterone
  • Tree shrew

ASJC Scopus subject areas

  • Pharmacology

Cite this

Czéh, B., Pudovkina, O., Van Der Hart, M. G. C., Simón, M., Heilbronner, U., Michaelis, T., ... Fuchs, E. (2005). Examining SLV-323, a novel NK1 receptor antagonist, in a chronic psychosocial stress model for depression. Psychopharmacology, 180(3), 548-557. https://doi.org/10.1007/s00213-005-2184-8

Examining SLV-323, a novel NK1 receptor antagonist, in a chronic psychosocial stress model for depression. / Czéh, Boldizsár; Pudovkina, Olga; Van Der Hart, Marieke G C; Simón, M.; Heilbronner, Urs; Michaelis, Thomas; Watanabe, Takashi; Frahm, Jens; Fuchs, Eberhard.

In: Psychopharmacology, Vol. 180, No. 3, 07.2005, p. 548-557.

Research output: Contribution to journalArticle

Czéh, B, Pudovkina, O, Van Der Hart, MGC, Simón, M, Heilbronner, U, Michaelis, T, Watanabe, T, Frahm, J & Fuchs, E 2005, 'Examining SLV-323, a novel NK1 receptor antagonist, in a chronic psychosocial stress model for depression', Psychopharmacology, vol. 180, no. 3, pp. 548-557. https://doi.org/10.1007/s00213-005-2184-8
Czéh, Boldizsár ; Pudovkina, Olga ; Van Der Hart, Marieke G C ; Simón, M. ; Heilbronner, Urs ; Michaelis, Thomas ; Watanabe, Takashi ; Frahm, Jens ; Fuchs, Eberhard. / Examining SLV-323, a novel NK1 receptor antagonist, in a chronic psychosocial stress model for depression. In: Psychopharmacology. 2005 ; Vol. 180, No. 3. pp. 548-557.
@article{c86cfa8f81a74b34974303cee0f63b79,
title = "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.",
keywords = "Antidepressant, Behavior, Hippocampus, Mood disorder, Neurogenesis, Proton magnetic resonance spectroscopy, Substance P, Testosterone, Tree shrew",
author = "Boldizs{\'a}r Cz{\'e}h and Olga Pudovkina and {Van Der Hart}, {Marieke G C} and M. Sim{\'o}n and Urs Heilbronner and Thomas Michaelis and Takashi Watanabe and Jens Frahm and Eberhard Fuchs",
year = "2005",
month = "7",
doi = "10.1007/s00213-005-2184-8",
language = "English",
volume = "180",
pages = "548--557",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Examining SLV-323, a novel NK1 receptor antagonist, in a chronic psychosocial stress model for depression

AU - Czéh, Boldizsár

AU - Pudovkina, Olga

AU - Van Der Hart, Marieke G C

AU - Simón, M.

AU - Heilbronner, Urs

AU - Michaelis, Thomas

AU - Watanabe, Takashi

AU - Frahm, Jens

AU - Fuchs, Eberhard

PY - 2005/7

Y1 - 2005/7

N2 - 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.

AB - 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.

KW - Antidepressant

KW - Behavior

KW - Hippocampus

KW - Mood disorder

KW - Neurogenesis

KW - Proton magnetic resonance spectroscopy

KW - Substance P

KW - Testosterone

KW - Tree shrew

UR - http://www.scopus.com/inward/record.url?scp=21344454706&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21344454706&partnerID=8YFLogxK

U2 - 10.1007/s00213-005-2184-8

DO - 10.1007/s00213-005-2184-8

M3 - Article

C2 - 15726334

AN - SCOPUS:21344454706

VL - 180

SP - 548

EP - 557

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 3

ER -