Naloxone antagonizes narcotic self blockade of emesis in the cat

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 the represented narcotic agents, moreover, naloxone thus administered 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, both antiemetic and emetic activities of the narcotic agents were essentially abolished, whereas apomorphine continued to evoke vomiting. In the presence of systemic naloxone, given to counteract self-blockade of vomiting, the narcotics were shown to induce vomiting through excitation of the medullary emetic chemoreceptor trigger zone and emetic receptor tolerance as well as cross-tolerance developed acutely. The present differentiation by naloxone of the emetic and antiemetic properties of narcotic agents placed in the cerebrospinal fluid 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.