title: Examining the clinical efficacy of bupropion and nortriptyline as smoking cessation agents in a rodent model of nicotine withdrawal.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Psychobiology Research Laboratories, School of Neurology, Neurobiology and Psychiatry, University of Newcastle, Newcastle Upon Tyne, UK.
authors: V C
authors: VC
authors: Wing
authors: M
authors: M
authors: Shoaib
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016642:Bupropion / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D008464:Mecamylamine; D009538:Nicotine / Q000009:adverse effects*; D009661:Nortriptyline / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D016540:Smoking Cessation; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000209:etiology; D014029:Tobacco Use Disorder / Q000188:drug therapy*
chemical_list: D000928:Antidepressive Agents; D016642:Bupropion; D008464:Mecamylamine; D009538:Nicotine; D009661:Nortriptyline
references: Psychopharmacology (Berl). 2002 Jul;162(2):156-67
references: 12110993
references: Clin Ther. 2001 May;23(5):744-52
references: 11394732
references: Pharmacol Biochem Behav. 1992 Nov;43(3):779-84
references: 1448472
references: J Pharmacol Exp Ther. 2000 Mar;292(3):1053-64
references: 10688623
references: Health Psychol. 1992;11(5):331-4
references: 1425551
references: Nature. 1998 May 7;393(6680):76-9
references: 9590692
references: Neuropharmacology. 1993 Oct;32(10):937-49
references: 8295716
references: Psychopharmacology (Berl). 1997 Feb;129(4):348-56
references: 9085404
references: J Psychiatry Neurosci. 1995 Jan;20(1):25-32
references: 7865498
references: Cochrane Database Syst Rev. 2007 Jan 24;(1):CD000031
references: 17253443
references: Cell Mol Neurobiol. 1999 Aug;19(4):467-89
references: 10379421
references: Addict Biol. 2005 Sep;10(3):219-31
references: 16109583
references: Arch Gen Psychiatry. 1986 Mar;43(3):289-94
references: 3954551
references: Ann Intern Med. 2001 Sep 18;135(6):423-33
references: 11560455
references: Pharmacol Biochem Behav. 1981 Jun;14(6):823-6
references: 7196048
references: J Clin Psychiatry. 1983 May;44(5 Pt 2):74-8
references: 6406468
references: Clin Pharmacol Ther. 2001 Jun;69(6):438-44
references: 11406741
references: Hosp Pract (1995). 1996 Oct 15;31(10):47-54, 57-9
references: 8859207
references: Psychopharmacology (Berl). 2003 Jul;168(3):347-58
references: 12698231
references: Brain Res. 1998 Jan 1;779(1-2):214-25
references: 9473676
references: J Pharmacol Exp Ther. 1998 Mar;284(3):1015-25
references: 9495862
references: Psychopharmacology (Berl). 2003 Aug;169(1):1-9
references: 12811464
references: Psychiatry Res. 2004 Apr 30;130(3):269-81
references: 15135160
references: Psychopharmacology (Berl). 1994 Jun;115(1-2):180-4
references: 7862893
references: Nature. 1978 Nov 9;276(5684):186-8
references: 216919
references: Br J Psychiatry. 1999 Feb;174:173-8
references: 10211174
references: N Engl J Med. 1999 Mar 4;340(9):685-91
references: 10053177
references: Prim Care. 1999 Sep;26(3):653-69
references: 10436292
references: Psychopharmacology (Berl). 2006 Mar;184(3-4):494-503
references: 16163521
references: Arch Gen Psychiatry. 1998 Aug;55(8):683-90
references: 9707377
references: Eur J Pharmacol. 2002 Jul 19;448(2-3):185-91
references: 12144940
references: Arch Intern Med. 1998 Oct 12;158(18):2035-9
references: 9778204
references: Proc Natl Acad Sci U S A. 1990 Oct;87(19):7522-6
references: 1977162
references: Am Fam Physician. 2005 Jan 1;71(1):67-8
references: 15663027
references: J Affect Disord. 1998 Dec;51(3):237-54
references: 10333980
references: Psychopharmacology (Berl). 2000 Jan;148(1):33-40
references: 10663415
references: Psychopharmacology (Berl). 1976 Oct 20;50(1):35-9
references: 827760
references: Pharmacol Biochem Behav. 2001 Dec;70(4):551-9
references: 11796153
references: J Clin Psychiatry. 1998;59 Suppl 4:66-72
references: 9554323
references: J Clin Psychiatry. 1995 Sep;56(9):395-401
references: 7665537
references: Psychopharmacology (Berl). 2003 Feb;165(4):405-12
references: 12451438
references: N Engl J Med. 1997 Oct 23;337(17):1195-202
references: 9337378
references: Arch Gen Psychiatry. 1991 Jan;48(1):52-9
references: 1984762
references: Naunyn Schmiedebergs Arch Pharmacol. 1994 May;349(5):443-6
references: 8065457
references: Synapse. 2003 Oct;50(1):20-8
references: 12872290
references: J Pharmacol Exp Ther. 2000 Oct;295(1):321-7
references: 10991997
references: Psychopharmacology (Berl). 1992;107(2-3):285-9
references: 1615127
references: Neuropsychopharmacology. 1999 Oct;21(4):560-74
references: 10481840
references: Psychopharmacology (Berl). 1999 Aug;145(4):370-7
references: 10460313
references: Am J Psychiatry. 2004 Nov;161(11):2100-7
references: 15514412