Examining the clinical efficacy of bupropion and nortriptyline as smoking cessation agents in a rodent model of nicotine withdrawal

Abstract

Rationale: At present, there is a lack of an established animal model to demonstrate the clinical efficacy of smoking cessation agents in the laboratory. The aim of this study was to compare the effects of the antidepressants bupropion and nortriptyline, clinically proven smoking cessation aids, within a rodent model of a nicotine withdrawal based on somatic measures.

Materials and methods: Male hooded Lister rats were chronically exposed to nicotine (3.16 mg kg1 day1) for 7 days via SC implanted ALZET osmotic minipumps. Animals were acutely pre-treated with bupropion (10, 30 or 60 mg/kg, IP) or nortriptyline (1.5, 4.7 and 15 mg/kg, IP), and nicotine withdrawal was precipitated by mecamylamine (1 mg/kg).

Results: Precipitation of nicotine withdrawal led to an increase in somatic signs including body shakes, chews, eye blinks, foot licks, head shakes and ptosis. Bupropion dose-dependently decreased the total abstinence scores and reduced the occurrence of some individual somatic signs. Pre-treatment with 60 mg/kg bupropion did not result in a significant increase in total abstinence scores or individual somatic signs scores after mecamylamine challenge, compared to the mecamylamine control group, suggesting nicotine withdrawal is fully attenuated at this dose. Similarly, the highest dose of nortriptyline reduced total abstinence scores and some individual somatic signs to the level of the mecamylamine control group. However, nortriptyline was only effective at alleviating somatic measures of withdrawal at doses which also suppressed locomotor activity.

Conclusion: In concurrence with clinical findings proposing alleviation of withdrawal states as a possible mechanism of bupropion and nortriptyline's smoking cessation action, both drugs were found to ameliorate somatic signs of nicotine withdrawal in rodents.