NALOXONE PRECIPITATES NICOTINE ABSTINENCE SYNDROME IN THE RAT

Recently, a rodent model of nicotine abstinence syndrome has been deve loped based on continuous subcutaneous infusion of nicotine tartrate a nd observing the frequency of spontaneous behavioral signs following t ermination of infusion. The observed signs closely resemble those comm only seen in rat opiate abstinence syndrome, raising the possibility t hat there is an endogenous opioid component in nicotine dependence. Th e present study demonstrates that the opiate antagonist naloxone can p recipitate an abstinence syndrome in nicotine-dependent rats. Fourteen rats were infused for 7 days with 9 mg/kg/day nicotine tartrate in sa line via an Alzet osmotic minipump. Fourteen rats were sham-operated a nd remained nicotine-naive. Half of each group received 4.5 mg/kg nalo xone SC immediately before a ''blind'' 15-min observation, while the o ther half received saline alone. ANOVA revealed significant nicotine i nfusion, naloxone injection and interaction effects. Post-hoc analysis showed that the nicotine-infused rats injected with naloxone had sign ificantly more signs than all other groups (P < 0.01). In a second exp eriment, 2 mg/kg morphine sulfate SC produced a significant (P < 0.01) 91.2% reduction of spontaneous abstinence signs observed 21 h after t ermination of nicotine infusion. These results are consistent with the hypothesized endogenous opioid component in nicotine dependence and a bstinence syndrome.