Assessment of antidepressant and anxiolytic properties of NK1 antagonists and Substance P in Wistar Kyoto rats

O. Malkesman, Y. Braw, A. Weller

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In an attempt to explore the involvement of substance P in depression and anxiety and its' potential therapeutic effects, we measured basal plasma and hypothalamic levels of substance P in a well-studied animal model of depression - adult male Wistar Kyoto (WKY) rats and their controls, Wistar rats. We also studied the influence of a substance P receptor (NK1) antagonist (SPA) on "anxiety-like" and "depressive-like" behaviors exhibited by the WKY rats in the open field and swim test paradigms, compared to controls. WKY rats exhibited lower levels of substance P compared to controls in the hypothalamus. Though the WKY strain exhibited less rearing behavior in the open field compared to controls, SPA did not influence this pattern of behavior. In contrast, SPA had a significant effect on a depressive-like behavior exhibited by the WKY strain - it reduced significantly the immobility duration of WKY rats in the swim test. Thus it seems that depression involves alterations in levels of substance P, and that NK1 antagonists may be effective in the relief of depressive, but not anxiety symptoms.

Original languageEnglish
Pages (from-to)619-625
Number of pages7
JournalPhysiology and Behavior
Issue number4
StatePublished - 16 Mar 2007

Bibliographical note

Funding Information:
The research reported in this paper was completed as part of the first author's PhD dissertation (OM in the Interdisciplinary Program in the Brain Sciences, Bar-Ilan University, Ramat-Gan, Israel). OM and YB were supported by President's fellowships, Bar-Ilan University. This research was supported by a grant from the Israel Science Foundation to A. Weller. Research in the Developmental Psychobiology lab was also partially supported by the Paula Rich Center, Bar-Ilan University.


  • Anxiety
  • Depression
  • Open field
  • Rat
  • Substance P
  • Swim test


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