INHALATION EXPOSURE TO VOLATILIZED OPIOIDS PRODUCES ANTINOCICEPTION IN MICE

The goal of this study was to determine whether opioids of varying pot encies are pharmacologically active via the inhalation route of admini stration in mice. The opioids evaluated included heroin, morphine, cod eine, fentanyl and meperidine; each of these drugs has the potential f or abuse in humans. Inhalation exposure to each of these compounds pro duced antinociception in a dose-dependent manner as assessed in the ta il-flick test. No pyrolysis products were detected after heating eithe r morphine or codeine at 250 degrees C for 5 min. Although 6-acetylmor phine was found after heating heroin, it accounted for less than 5% of the recovered sample. Heroin was somewhat less potent by inhalation a dministration than i.v. injection, with ED(50) values of 1.6 and 0.69 mu mol/kg, respectively. In contrast, the relative potency of morphine was substantially greater when inhaled than when injected, with respe ctive ED(50) values of 0.77 and 3.9 mu mol/kg. Whereas the body to bra in ratios of [H-3]morphine were approximately 8 and 20 for inhalation exposure and i.v. injection, respectively, the ratio for heroin was ap proximately 5 regardless of administration route. This pattern of resu lts suggests that the increase in morphine potency upon inhalation may have resulted from an increased accessibility to the brain compared w ith i.v. injection. Finally, naloxone reversed the antinociceptive eff ects of volatilized heroin, but neither the kappa selective antagonist nor-binaltorphimine nor the delta selective antagonist naltrindole bl ocked this antinociception, which suggests the involvement of mu opioi d receptors. These findings taken together suggest the potential for t he abuse of a variety of opioids, in addition to heroin, through the i nhalation route of administration by humans.