title: Inhibition of monoamine oxidase isoforms modulates nicotine withdrawal syndrome in the rat.
abstract: OBJECTIVE
  There have been many reports of monoamine oxidase (MAO) inhibition by non-nicotine ingredients in tobacco smoke, persisting for days after smoking cessation. This study determined the effect of inhibiting MAO and its isoforms on nicotine withdrawal syndrome.
  
  
  METHODS
  Rats were rendered nicotine-dependent by seven days of subcutaneous (s.c.) 9 mg/kg/day infusion of nicotine bitartrate. Twenty-two hours after termination of infusion, they were observed over 20 min for somatically expressed nicotine withdrawal signs. Three hours before observation, rats were injected intraperitoneally (i.p.) with 4 mg/kg each of the MAO A antagonist clorgyline and the MAO B antagonist deprenyl, or with saline alone. A similar experiment was performed with non-dependent, saline-infused rats. Another experiment compared nicotine-dependent rats that received injections of either saline or 4 mg/kg clorgyline alone. A further experiment compared rats receiving either saline or 4 mg/kg deprenyl alone.
  
  
  RESULTS
  Combined treatment with both MAO inhibitors markedly and significantly exacerbated somatically expressed nicotine withdrawal signs in nicotine infused rats, while having no significant effects in saline-infused rats. Rats injected s.c. with 4 mg/kg clorgyline alone had significantly more withdrawal signs than saline-injected rats, while deprenyl-injected rats had significantly fewer signs than saline controls. Assays confirmed that clorgyline thoroughly reduced MAO A enzymatic activity and deprenyl thoroughly reduced MAO B activity.
  
  
  CONCLUSIONS
  The results suggest that inhibition of MAO A may contribute to the intensity of withdrawal syndrome in smoking cessation.
authors.affiliation: University of Houston-Clear Lake, Houston, TX, USA. Electronic address: malin@uhcl.edu.
authors.forename: D H
authors.initials: DH
authors.lastname: Malin
authors.forename: W D
authors.initials: WD
authors.lastname: Moon
authors.forename: P
authors.initials: P
authors.lastname: Goyarzu
authors.forename: E
authors.initials: E
authors.lastname: Barclay
authors.forename: N
authors.initials: N
authors.lastname: Magallanes
authors.forename: A J
authors.initials: AJ
authors.lastname: Vela
authors.forename: A P
authors.initials: AP
authors.lastname: Negrete
authors.forename: H
authors.initials: H
authors.lastname: Mathews
authors.forename: B
authors.initials: B
authors.lastname: Stephens
authors.forename: W R
authors.initials: WR
authors.lastname: Mills
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D003010:Clorgyline / Q000008:administration & dosage*; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage*; D009538:Nicotine / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000008:administration & dosage*; D016540:Smoking Cessation; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000201:enzymology
chemical_list: D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D009538:Nicotine; D008995:Monoamine Oxidase; D003010:Clorgyline
keywords: Clorgyline; Deprenyl; MAO inhibitors; Monoamine oxidase inhibition; Nicotine withdrawal