, Volume 178, Issue 2–3, pp 115–124 | Cite as

Neuropeptide expression in rats exposed to chronic mild stresses

  • Valeriy Sergeyev
  • Serguei Fetissov
  • Aleksander A. Mathé
  • Patricia A. Jimenez
  • Tamas Bartfai
  • Patrick Mortas
  • Laurent Gaudet
  • Jean-Luc Moreau
  • Tomas Hökfelt
Original Investigation


To investigate a possible link between some neuropeptides and depression, we analyzed their mRNA levels in brains of rats exposed to chronic mild stresses (CMS; a stress-induced anhedonia model), a commonly used model of depression. Rats exposed for 3 weeks to repeated, unpredictable, mild stressors exhibited an increased self-stimulation threshold, reflecting the development of an anhedonic state, which is regarded as an animal model of major depression. In situ hybridization was employed to monitor mRNA levels of neuropeptide Y (NPY), substance P and galanin in several brain regions. In the CMS rats, NPY mRNA expression levels were significantly decreased in the hippocampal dentate gyrus but increased in the arcuate nucleus. The substance P mRNA levels were increased in the anterodorsal part of the medial amygdaloid nucleus, in the ventromedial and dorsomedial hypothalamic nuclei and the lateral hypothalamic area, whereas galanin mRNA levels were decreased in the latter two regions. These findings suggest a possible involvement of these three peptides in mechanisms underlying depressive disorders and show that similar peptide changes previously demonstrated in genetic rat models also occur in the present stress-induced anhedonia model.


Depression Galanin Mood Neuropeptide Neuropeptide Y Substance P 



Chronic mild stress


Flinders resistant line


Flinders sensitive line


Neuropeptide tyrosine (Y)


Rapid eye movement



This study was supported by the Swedish Research Council, Mariannne and Marcus Wallenberg’s Foundation and the EU (QLK3-CT-2000-00237; NEWMOOD, LSHM-CT-2003-503474). S.F. was supported by the Wenner-Gren Foundations.


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Valeriy Sergeyev
    • 1
  • Serguei Fetissov
    • 1
  • Aleksander A. Mathé
    • 2
  • Patricia A. Jimenez
    • 2
  • Tamas Bartfai
    • 3
    • 4
  • Patrick Mortas
    • 3
  • Laurent Gaudet
    • 3
  • Jean-Luc Moreau
    • 3
  • Tomas Hökfelt
    • 1
  1. 1.Department of NeuroscienceKarolinska InstitutetStockholmSweden
  2. 2.Department of Physiology and PharmacologyKarolinska InstitutetStockholmSweden
  3. 3.Pharmaceutical Division, Preclinical CNS ResearchF. Hoffmann-La Roche Ltd.BaselSwitzerland
  4. 4.The Harold Dorris Neurological InstituteThe Scripps InstituteLa JollaUSA

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