title: Nicotine self-administration and reinstatement of nicotine-seeking in male and female rats.
abstract: BACKGROUND
  Tobacco addiction is a relapsing disorder that constitutes a substantial worldwide health problem, with evidence suggesting that nicotine and nicotine-associated stimuli play divergent roles in maintaining smoking behavior in men and women. While animal models of tobacco addiction that utilize nicotine self-administration have become more widely established, systematic examination of the multiple factors that instigate relapse to nicotine-seeking have been limited. Here, we examined nicotine self-administration and subsequent nicotine-seeking in male and female Sprague-Dawley rats using an animal model of self-administration and relapse.
  
  
  METHODS
  Rats lever pressed for nicotine (0.03 and 0.05 mg/kg/infusion, IV) during 15 daily 2-h sessions, followed by extinction of lever responding. Once responding was extinguished, we examined the ability of previously nicotine-paired cues (tone+light), the anxiogenic drug yohimbine (2.5mg/kg, IP), a priming injection of nicotine (0.3mg/kg, SC), or combinations of drug+cues to reinstate nicotine-seeking.
  
  
  RESULTS
  Both males and females readily acquired nicotine self-administration and displayed comparable levels of responding and intake at both nicotine doses. Following extinction, exposure to the previously nicotine-paired cues or yohimbine, but not the nicotine-prime alone, reinstated nicotine-seeking in males and females. Moreover, when combined with nicotine-paired cues, both yohimbine and nicotine enhanced reinstatement. No significant sex differences or estrous cycle dependent changes were noted across reinstatement tests.
  
  
  CONCLUSIONS
  These results demonstrate the ability to reinstate nicotine-seeking with multiple modalities and that exposure to nicotine-associated cues during periods of a stressful state or nicotine can increase nicotine-seeking.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Feltenstein
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Ghee
authors.forename: Ronald E
authors.initials: RE
authors.lastname: See
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D005260:Female; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration; D014029:Tobacco Use Disorder / Q000523:psychology*
chemical_list: D009538:Nicotine