Pharmacological characterization of senktide-induced tail whips

The tachykinin NK3 receptor shows promise as a novel target for antipsychotics, but knowledge of downstream activity following tachykinin NK3 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 NK3 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 NK3 receptor specificity was confirmed by the absence of the senktide-induced tail whip response in tachykinin NK3 receptor knockout mice. Effects of tachykinin receptor pharmacological agents were tested by pretreatment with tachykinin NK3 receptor antagonists (SB222200, talnetant and osanetant), which attenuated senktide-induced tail whips, and the tachykinin NK1 receptor antagonist MK869, which had no effect on senktide-induced tail whips. Pharmacological interactions with other neurotransmitter systems were determined by pretreatment with dopamine D1, D2, and D3 receptor antagonists, atypical antipsychotics, serotonin 5HT1a receptor antagonists, serotonin 5HT2a/c receptor antagonists, benzodiazepine and putative anxiolytics, antidepressants, and an anticholinergic. Senktide-induced tail whips were attenuated by dopamine D2 receptor antagonists, atypical antipsychotics, serotonin 5HT2a/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 NK3 receptor, and provides valuable information on the downstream pharmacology of tachykinin NK3 receptor activation.