title: Bupropion and its main metabolite reverse nicotine chronic tolerance in the mouse.
abstract: BACKGROUND
  Although the antidepressant bupropion is prescribed to aid in smoking cessation, little is known concerning its mechanisms of action in this regard. One factor that might influence quit success is nicotine tolerance, which could promote high levels of nicotine intake in order to maintain nicotine's subjective effects (thereby making attempts to reduce smoking more difficult).
  
  
  METHODS
  To explore whether bupropion and its active hydroxymetabolite modulate nicotine tolerance, mice were injected for 14 days with saline or nicotine. On Day 14, animals received saline, (2S,3S)-hydroxybupropion, or bupropion at different doses. On Day 15, mice were assayed on test day for nicotine-induced analgesia and hypothermia.
  
  
  RESULTS
  Animals chronically injected with saline + nicotine developed tolerance to nicotine's effects in both assays. Administration of bupropion and (2S,3S)-hydroxybupropion dose-dependently reversed chronic nicotine tolerance.
  
  
  CONCLUSIONS
  These results indicate that bupropion's ability to promote smoking cessation may be partly due to its attenuation of nicotine tolerance since both measured responses of nicotine (antinociception and hypothermia) are mediated to a large extent by neuronal α4β2* nicotine receptors.
authors.affiliation: Department of Pharmacology & Toxicology, Virginia Commonwealth University Medical Campus, Richmond, VA 23298-0524, USA.
authors.forename: Sheri D
authors.initials: SD
authors.lastname: Grabus
authors.forename: Frank Ivy
authors.initials: FI
authors.lastname: Carroll
authors.forename: Mohamad Imad
authors.initials: MI
authors.lastname: Damaj
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D016642:Bupropion / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D007036:Hypothermia, Induced; D008297:Male; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D016540:Smoking Cessation / Q000379:methods
chemical_list: D000700:Analgesics; D000928:Antidepressive Agents; C580748:hydroxybupropion; D016642:Bupropion; D009538:Nicotine