title: Attenuation by baclofen of nicotine rewarding properties and nicotine withdrawal manifestations.
abstract: BACKGROUND
  Nicotine is a major active ingredient in tobacco and plays a major role in tobacco addiction. In rodents, repeated nicotine administration produces behavioral responses related to its addictive properties, such as reinforcing effects and physical dependence.
  
  
  OBJECTIVE
  The aim of the present study was to evaluate the possible role of GABAB receptor in responses induced by repeated nicotine administration in Swiss Webster mice.
  
  
  RESULTS
  Nicotine hydrogen tartrate salt (0.5 mg/kg, s.c.) administration induced rewarding properties in the conditioning place preference test. The GABAB receptor agonist, baclofen (3 mg/kg, i.p.) abolished the rewarding properties induced by nicotine hydrogen tartrate salt (0.5 mg/kg, s.c.). In addition, naloxone-precipitated nicotine withdrawal induced somatic manifestations, anxiety-like effects in the elevated plus maze test and dysphoric manifestations in the conditioned place aversion paradigm. Baclofen (2 and 3 mg/kg, i.p.) prevented the somatic manifestations and the anxiety-like effects associated with naloxone-precipitated nicotine withdrawal but not the dysphoric manifestations.
  
  
  CONCLUSIONS
  These results showed that nicotine rewarding properties and negative aspects of nicotine withdrawal, such as anxiety-like effects and somatic manifestations, can be modulated by the GABAB receptor activity. This study now reveals a novel possible application of baclofen to develop new therapeutic strategies to achieve smoking cessation.
authors.affiliation: Instituto de Investigaciones Farmacológicas (CONICET), Junín 956 5° Piso, Buenos Aires, C1113AAD, Argentina.
authors.forename: Andrés P
authors.initials: AP
authors.lastname: Varani
authors.forename: Ester
authors.initials: E
authors.lastname: Aso
authors.forename: Lirane Machado
authors.initials: LM
authors.lastname: Moutinho
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
authors.forename: Graciela N
authors.initials: GN
authors.lastname: Balerio
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001418:Baclofen / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009068:Movement / Q000187:drug effects / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D018080:Receptors, GABA-B / Q000378:metabolism; D012201:Reward; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D014029:Tobacco Use Disorder / Q000188:drug therapy
chemical_list: D058786:GABA-B Receptor Agonists; D009292:Narcotic Antagonists; D018722:Nicotinic Agonists; D018080:Receptors, GABA-B; D009270:Naloxone; D009538:Nicotine; D001418:Baclofen