title: Tobacco smoke exposure induces nicotine dependence in rats.
abstract: BACKGROUND
  Tobacco smoke contains nicotine and many other compounds that act in concert on the brain reward system. Therefore, animal models are needed that allow the investigation of chronic exposure to the full spectrum of tobacco smoke constituents.
  
  
  OBJECTIVE
  The aim of these studies was to investigate if exposure to tobacco smoke leads to nicotine dependence in rats.
  
  
  METHODS
  The intracranial self-stimulation procedure was used to assess the negative affective aspects of nicotine withdrawal. Somatic signs were recorded from a checklist of nicotine abstinence signs. Nicotine self-administration sessions were conducted to investigate if tobacco smoke exposure affects the motivation to self-administer nicotine. Nicotinic receptor autoradiography was used to investigate if exposure to tobacco smoke affects central alpha7 nicotinic acetylcholine receptor (nAChR) and non-alpha7 nAChR levels (primarily alpha4beta2 nAChRs).
  
  
  RESULTS
  The nAChR antagonist mecamylamine dose-dependently elevated the brain reward thresholds of the rats exposed to tobacco smoke and did not affect the brain reward thresholds of the untreated control rats. Furthermore, mecamylamine induced more somatic withdrawal signs in the smoke-exposed rats than in the control rats. Nicotine self-administration was decreased 1 day after the last tobacco smoke exposure sessions and was returned to control levels 5 days later. Tobacco smoke exposure increased the alpha7 nAChR density in the CA2/3 area and the stratum oriens and increased the non-alpha7 nAChR density in the dentate gyrus.
  
  
  CONCLUSIONS
  Tobacco smoke exposure leads to nicotine dependence as indicated by precipitated affective and somatic withdrawal signs and induces an upregulation of nAChRs in the hippocampus.
authors: Department of Psychiatry, College of Medicine, McKnight Brain Institute, University of Florida, 100 S. Newell Dr., PO Box 100256, Gainesville, FL 32610, USA.
authors: Elysia
authors: E
authors: Small
authors: Hina P
authors: HP
authors: Shah
authors: Jake J
authors: JJ
authors: Davenport
authors: Jacqueline E
authors: JE
authors: Geier
authors: Kate R
authors: KR
authors: Yavarovich
authors: Hidetaka
authors: H
authors: Yamada
authors: Sreedharan N
authors: SN
authors: Sabarinath
authors: Hartmut
authors: H
authors: Derendorf
authors: James R
authors: JR
authors: Pauly
authors: Mark S
authors: MS
authors: Gold
authors: Adrie W
authors: AW
authors: Bruijnzeel
mesh_terms: D000818:Animals; D001345:Autoradiography; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage / Q000494:pharmacology; D009042:Motivation; D009538:Nicotine / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012646:Self Administration; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014029:Tobacco Use Disorder / Q000209:etiology*; D015854:Up-Regulation / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579165:Chrna7 protein, rat; D011978:Receptors, Nicotinic; D014028:Tobacco Smoke Pollution; D064569:alpha7 Nicotinic Acetylcholine Receptor; D008464:Mecamylamine; D009538:Nicotine