Examining the clinical efficacy of bupropion and nortriptyline as smoking cessation agents in a rodent model of nicotine withdrawal
- First Online:
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).
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.
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.
KeywordsNicotine Withdrawal Rodent Bupropion Nortriptyline
- Brody AL, Mandelkern MA, Lee G, Smith E, Sadeghi M, Saxena S, Jarvik ME, London ED (2004) Attenuation of cue-induced cigarette craving and anterior cingulate cortex activation in bupropion-treated smokers: a preliminary study. Psychiatry Research 130:269–281 (erratum appears in Psychiatry Res. 2004 Dec 15;132(2):183–4)PubMedCrossRefGoogle Scholar
- Goldstein MG (1998) Bupropion sustained release and smoking cessation. J Clin Psychiatry 4:66–72Google Scholar
- Gonzales DH, Nides MA, Ferry LH, Kustra RP, Jamerson BD, Segall N, Herrero LA, Krishen A, Sweeney A, Buaron K, Metz A (2001) Bupropion SR as an aid to smoking cessation in smokers treated previously with bupropion: a randomized placebo-controlled study. Clin Pharmacol Ther 69:438–444PubMedCrossRefGoogle Scholar
- Hughes JR, Stead LF, Lancaster T (2007) Antidepressants for smoking cessation. [update in Cochrane Database of Syst Rev. 2007; (1): CD000031; PMID:14651858]. Cochrane Database of Systematic ReviewsGoogle Scholar
- Jamerson BD, Nides M, Jorenby DE, Donahue R, Garrett P, Johnston JA, Fiore MC, Rennard SI, Leischow SJ (2001) Late-term smoking cessation despite initial failure: an evaluation of bupropion sustained release, nicotine patch, combination therapy, and placebo. Clin Ther 23:744–752PubMedCrossRefGoogle Scholar
- Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, Smith SS, Muramoto ML, Daughton DM, Doan K, Fiore MC, Baker TB (1999) A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation.[see comment]. N Engl J Med 340:685–691PubMedCrossRefGoogle Scholar
- Leshner AI (1996) Understanding drug addiction: implications for treatment [see comment]. Hosp Pract 31:47–54Google Scholar