Original Investigation

Psychopharmacology

, Volume 178, Issue 2, pp 115-124

Neuropeptide expression in rats exposed to chronic mild stresses

  • Valeriy SergeyevAffiliated withDepartment of Neuroscience, Karolinska Institutet
  • , Serguei FetissovAffiliated withDepartment of Neuroscience, Karolinska Institutet
  • , Aleksander A. MathéAffiliated withDepartment of Physiology and Pharmacology, Karolinska Institutet
  • , Patricia A. JimenezAffiliated withDepartment of Physiology and Pharmacology, Karolinska Institutet
  • , Tamas BartfaiAffiliated withPharmaceutical Division, Preclinical CNS Research, F. Hoffmann-La Roche Ltd.The Harold Dorris Neurological Institute, The Scripps Institute
  • , Patrick MortasAffiliated withPharmaceutical Division, Preclinical CNS Research, F. Hoffmann-La Roche Ltd.
  • , Laurent GaudetAffiliated withPharmaceutical Division, Preclinical CNS Research, F. Hoffmann-La Roche Ltd.
  • , Jean-Luc MoreauAffiliated withPharmaceutical Division, Preclinical CNS Research, F. Hoffmann-La Roche Ltd.
  • , Tomas HökfeltAffiliated withDepartment of Neuroscience, Karolinska Institutet Email author 

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Abstract

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.

Keywords

Depression Galanin Mood Neuropeptide Neuropeptide Y Substance P