The emetic and anti-emetic effects of the capsaicin analogue resiniferatoxin in Suncus murinus the house musk shrew

摘要

class="enumerated" style="list-style-type:decimal">In Suncus murinus the ultrapotent capsaicin analogue resiniferatoxin (RTX) induced an emetic response in the dose range 1–1000 μg kg⁻¹, s.c. The latency was inversely related to dose and ranged from 41.2±4.4 min. (1 μg kg⁻¹, s.c.) to 2.7±0.6 min. (1000 μg kg⁻¹, s.c.).The emetic response to RTX (10 or 100 μg kg⁻¹, s.c.) was blocked or markedly reduced by pre-treatment with RTX (100 μg kg⁻¹, s.c.), 8-OH-DPAT (100 μg kg⁻¹, s.c.), morphine (2 mg kg⁻¹, s.c.), neonatal capsaicin (100 mg kg⁻¹, s.c.) and the NK1 receptor antagonist CP-99,994 (10–20 mg kg⁻¹, s.c.) but not by the 5-HT3 receptor antagonist tropisetron (200 μg kg⁻¹, s.c.).RTX (100 μg kg⁻¹, s.c.) induced c-fos-like immunoreactivity in the area postrema and parts of the nucleus tractus solitarius. This pattern is consistent with the proposal that the emetic effect is mediated via one or both of these structures and an involvement of substance P is discussed.RTX (10 and 100 μg kg⁻¹, s.c.) had broad-spectrum antiemetic effects in Suncus as indicated by its ability to block or markedly reduce the emetic response to motion (1 Hz, 4 cm lateral, 10 min.), cisplatin (20 mg kg⁻¹, i.p.), intragastric copper sulphate (40 mg kg⁻¹, p.o.), nicotine (10 mg kg⁻¹, s.c.) and RTX (100 μg kg⁻¹, s.c.) itself.It is proposed that the site of the anti-emetic effect is in the nucleus tractus solitarius and mechanisms involving the modulation of substance P release are discussed.The general utility of Suncus for investigations of vanilloid receptors is reviewed in the light of the exquisite sensitivity of the emetic reflex in this species to resiniferatoxin.