resiniferatoxin and Motion-Sickness

The emetic (retching and vomiting) reflex is an important component of the body's defence system against accidentally ingested toxins and emesis is also a common symptom of disease and a side-effect of a number of pharmacological therapies. The development of the reflex has been the subject of few systematic studies. The aim of this study was to characterise the development of the emetic reflex in Suncus murinus (the house musk shrew) using emetic stimuli acting via three different afferent pathways: motion via the vestibular system, pyrogallol via abdominal vagal afferents and resiniferatoxin (a capsaicin analog) via the brainstem. The emetic reflex was not present to any stimulus prior to postnatal day 10 but the onset of the response to motion lagged behind that to the other stimuli in not being present until postnatal day 15. Body weight was not a determinant of the presence of the reflex. It is proposed that the delayed presence of the emetic reflex in Suncus makes it an ideal species in which to investigate factors regulating its development.

Topics: Age Factors; Animals; Body Weight; Diterpenes; Female; Male; Motion Sickness; Neurotoxins; Pyrogallol; Reflex; Shrews; Solitary Nucleus; Substance P; Vagus Nerve; Vestibule, Labyrinth; Vomiting

1. In SUNCUS: murinus the ultrapotent capsaicin analogue resiniferatoxin (RTX) induced an emetic response in the dose range 1 - 1000 microg kg(-1), s.c. The latency was inversely related to dose and ranged from 41.2+/-4.4 min. (1 microg kg(-1), s.c.) to 2.7+/-0.6 min. (1000 microg kg(-1), s.c.). 2. The emetic response to RTX (10 or 100 microg kg(-1), s.c.) was blocked or markedly reduced by pre-treatment with RTX (100 microg kg(-1), s.c.), 8-OH-DPAT (100 microg kg(-1), s.c.), morphine (2 mg kg(-1), s.c.), neonatal capsaicin (100 mg kg(-1), s.c.) and the NK(1) receptor antagonist CP-99,994 (10 - 20 mg kg(-1), s.c.) but not by the 5-HT(3) receptor antagonist tropisetron (200 microg kg(-1), s.c.). 3. RTX (100 microg 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. 4. RTX (10 and 100 microg 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 microg kg(-1), s.c.) itself. 5. 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. 6. 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.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Abdomen; Animals; Animals, Newborn; Antiemetics; Behavior, Animal; Capsaicin; Cisplatin; Copper Sulfate; Diterpenes; Dose-Response Relationship, Drug; Female; Indoles; Injections, Intraventricular; Male; Medulla Oblongata; Morphine; Motion Sickness; Nicotine; Piperidines; Proto-Oncogene Proteins c-fos; Serotonin Receptor Agonists; Shrews; Tropisetron; Vagotomy; Vomiting