NALOXONE ANTAGONIZES NARCOTIC SELF-BLOCKADE OF EMESIS IN CAT

Abstract

Morphine, levorphanol, fentanyl and methadone given by intracerebroventricular (i.c.v.) injection blocked the vomiting response to a standard emetic test dose of apomorphine subsequently injected i.c.v. Of these narcotics, only morphine initially evoked vomiting. Systemic pretreatment with naloxone (5 mg/kg i.p. or i.v.) uniformly abolished the antiemetic activity of all represented narcotic agents; naloxone was followed consistently by emetic responses to those narcotics which separately failed to evoke vomiting. When naloxone was injected i.c.v. in addition to being given systemically, antiemetic and emetic activities of the narcotic agents were essentially abolished; apomorphine continued to evoke vomiting. In the presence of systemic naloxone, given to counteract self-blockade of vomiting, the narcotics induced vomiting through excitation of the medullary emetic chemoreceptor trigger zone and emetic receptor tolerance and cross-tolerance developed acutely. The present differentiation by naloxone of the emetic and antiemetic properties of narcotic agents placed in the CSF indicates that the opposing narcotic actions are exercised at different sites in the brain, and that the narcotic receptor specificity of the chemoreceptor trigger zone does not encompass the emetic action of apomorphine.