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Pharmacological characterization of senktide-induced tail whips.

Authors
  • Nordquist, Rebecca E1
  • Ballard, Theresa M
  • Algeyer, Brigitte
  • Pauly-Evers, Meike
  • Ozmen, Laurence
  • Spooren, Will
  • 1 F. Hoffmann-La Roche Ltd, Pharma Research Basel Discovery, Neuroscience, Building 72-148, CH-4070 Basel, Switzerland. [email protected] , (Switzerland)
Type
Published Article
Journal
Neuropharmacology
Publication Date
January 2010
Volume
58
Issue
1
Pages
259–267
Identifiers
DOI: 10.1016/j.neuropharm.2009.04.018
PMID: 19540857
Source
Medline
License
Unknown

Abstract

The tachykinin NK(3) receptor shows promise as a novel target for antipsychotics, but knowledge of downstream activity following tachykinin NK(3) receptor activation is lacking. To determine the practical utility of senktide-induced tail whips in mice as a tool for determining and characterizing downstream activity following tachykinin NK(3) receptor activation, mice were injected with 0.05 nmol of senktide i.c.v. and the number of tail whip bouts was counted for 20 min. Strain differences were observed, with NMRI mice showing a stronger tail whip response than C57Bl/6J mice. Tachykinin NK(3) receptor specificity was confirmed by the absence of the senktide-induced tail whip response in tachykinin NK(3) receptor knockout mice. Effects of tachykinin receptor pharmacological agents were tested by pretreatment with tachykinin NK(3) receptor antagonists (SB222200, talnetant and osanetant), which attenuated senktide-induced tail whips, and the tachykinin NK(1) receptor antagonist MK869, which had no effect on senktide-induced tail whips. Pharmacological interactions with other neurotransmitter systems were determined by pretreatment with dopamine D(1), D(2), and D(3) receptor antagonists, atypical antipsychotics, serotonin 5HT(1a) receptor antagonists, serotonin 5HT(2a/c) receptor antagonists, benzodiazepine and putative anxiolytics, antidepressants, and an anticholinergic. Senktide-induced tail whips were attenuated by dopamine D(2) receptor antagonists, atypical antipsychotics, serotonin 5HT(2a/c) antagonists, and benzodiazepine anxiolytics, but unaffected by drugs from other classes. Thus, the senktide-induced tail whip response is easily quantifiable, specific to the tachykinin NK(3) receptor, and provides valuable information on the downstream pharmacology of tachykinin NK(3) receptor activation.

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