Nicotine alleviation of nicotine abstinence syndrome is naloxone-reversible.

In a recently introduced rodent model of nicotine abstinence syndrome, the observed signs closely resembled those typical of rat opiate abstinence syndrome. Signs were precipitated by naloxone and potently reversed by morphine as well as nicotine itself, suggesting that nicotine might relieve nicotine abstinence syndrome through releasing endogenous opioids. To test this hypothesis, rats were continuously infused subcutaneously (SC) for 7 days with 9 mg/kg per day nicotine tartrate. Each rat was observed for abstinence signs at 18 and 21 h after termination of infusion. Three minutes before the 21-h test, all rats received 0.35 mg/kg nicotine tartrate, SC; 5 min before the nicotine injection, subjects received 9 or 4.5 mg/kg naloxone or saline alone, SC. Abstinence reversal scores were calculated as signs at 21 h as a percentage of signs at 18 h. Naloxone prevented nicotine alleviation of nicotine abstinence in a dose-related manner. However, naloxone in the absence of a nicotine injection had no effect on abstinence severity in either highly dependent or moderately dependent rats (infused with 9 or 5 mg/kg per day nicotine tartrate, respectively). These results support the hypothesis that endogenous opioids play a role in nicotine dependence and abstinence.

The nicotinic antagonist mecamylamine precipitates nicotine abstinence syndrome in the rat.

Recently, a rodent model of nicotine abstinence syndrome has been developed based on observing the frequency of spontaneous behavioral signs following termination of continuous subcutaneous infusion of nicotine tartrate. In the present study, the nicotinic antagonist mecamylamine precipitated an abstinence syndrome in nicotine-dependent rats. Twelve rats were each infused for 7 days with 9 mg/kg per day nicotine tartrate in saline via Alzet osmotic minipumps; another 12 rats were sham-operated and remained nicotine-naive. Six rats from each group received 1 mg/kg mecamylamine in saline SC immediately before a 30-min observation, while the remaining six rats from each group received saline alone. Nicotine-infused rats receiving mecamylamine exhibited significantly more (P < 0.01), overall abstinence signs than all other groups. In terms of categories of signs, they displayed significantly more gasps/writhes, teeth chatter/chews, shakes/tremors and ptosis. In a second experiment utilizing only nicotine-naive rats, a far higher dose of mecamylamine (5 mg/kg sc) induced a quasi-nicotine abstinence syndrome. The results provide further validation for this rodent model of nicotine abstinence syndrome.

Naloxone precipitates nicotine abstinence syndrome in the rat.

Recently, a rodent model of nicotine abstinence syndrome has been developed based on continuous subcutaneous infusion of nicotine tartrate and observing the frequency of spontaneous behavioral signs following termination of infusion. The observed signs closely resemble those commonly seen in rat opiate abstinence syndrome, raising the possibility that there is an endogenous opioid component in nicotine dependence. The present study demonstrates that the opiate antagonist naloxone can precipitate an abstinence syndrome in nicotine-dependent rats. Fourteen rats were infused for 7 days with 9 mg/kg/day nicotine tartrate in saline via an Alzet osmotic minipump. Fourteen rats were sham-operated and remained nicotine-naive. Half of each group received 4.5 mg/kg naloxone SC immediately before a "blind" 15-min observation, while the other half received saline alone. ANOVA revealed significant nicotine infusion, naloxone injection and interaction effects. Post-hoc analysis showed that the nicotine-infused rats injected with naloxone had significantly more signs than all other groups (P < 0.01). In a second experiment, 2 mg/kg morphine sulfate SC produced a significant (P < 0.01) 91.2% reduction of spontaneous abstinence signs observed 21 h after termination of nicotine infusion. These results are consistent with the hypothesized endogenous opioid component in nicotine dependence and abstinence syndrome.

Subcutaneous injection of an analog of neuropeptide FF precipitates morphine abstinence syndrome.

Neuropeptide FF (NPFF) has been shown to exert various antiopiate actions, including precipitation of opiate abstinence syndrome by third ventricle injection in morphine dependent rats. In the present study, dansyl-Pro-Gln-Arg-Phe-amide, a lipophilic analog of NPFF, was injected into morphine dependent rats and appropriate sham controls at a dose of 9 mg/kg s.c. Comparison groups were injected with ethanol/water vehicle alone. The NPFF analog precipitated a vigorous opiate abstinence syndrome in morphine dependent rats, but not in sham controls.

Rodent model of nicotine abstinence syndrome.

Few animals models are currently in use for the recognized clinical problem of nicotine dependence and abstinence. This study introduces a rapid and convenient model using the rat. Sixteen male rats were rendered nicotine dependent by 7 days of continuous subcutaneous infusion of either 3 mg/kg/day (n = 8) or 9 mg/kg/day (n = 8) nicotine tartrate salt; 8 control rats were infused with saline alone. Rats were observed for 15 min before, during, and after the drug infusion period using a tally sheet modified from a standard checklist of opiate abstinence signs. There were few signs observed in any group at baseline and at the end of the infusion period. However, nicotine-infused rats showed a significant, dose-related increase over the control group at 16 h after the end of infusion, largely subsiding by 40 h. The most frequently observed signs during withdrawals included: teeth-chattering/chews, writhes/gasps, ptosis, tremors/shakes, and yawns. A significant drop in locomotor activity and increase in weight gain following termination of nicotine infusion provided additional evidence of an abstinence syndrome. This syndrome was alleviated by SC administration of 0.4 mg/kg nicotine tartrate.