title: Sex differences in the contribution of nicotine and nonpharmacological stimuli to nicotine self-administration in rats.
abstract: BACKGROUND
  Sex differences have been reported for the impact of nicotine and nonpharmacological cues on smoking. While nonpharmacological environmental stimuli have also been shown to influence nicotine self-administration in rats, there have been no attempts to examine the impact of sex differences in the contributions of nicotine and nondrug stimuli to this behavior.
  
  
  OBJECTIVE
  This experiment investigated sex differences in operant responding for nicotine in rats when drug infusions were delivered either in the absence of, or in combination with, a nonpharmacological stimulus.
  
  
  METHODS
  Initially, male and female rats acquired self-administration for nicotine alone across a range of doses (0.03, 0.06, and 0.15 mg kg(-1) inf(-1), freebase). After stable acquisition, nicotine infusions were combined with a weakly reinforcing, compound visual stimulus.
  
  
  RESULTS
  While there was no overall effect of dose on active lever responding for nicotine in the absence of the visual stimulus, female rats responded more on the reinforced lever than males at 0.06 and 0.15 mg kg(-1) inf(-1) on an FR5 schedule. However, they also showed increased responding on the nonreinforced lever compared to males at the same doses. Combining nicotine infusions with the visual stimulus doubled responding compared to nicotine alone at 0.03 and 0.06, but not at 0.15 mg kg(-1) inf(-1): this effect was significantly greater for female rats.
  
  
  CONCLUSIONS
  These data highlight the prominent contribution of nonpharmacological stimuli to nicotine-reinforced behavior across a range of doses in both male and female rats. They also reveal sex differences in operant responding for nicotine under conditions where a nonpharmacological stimulus is either absent, or combined with drug delivery.
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA. nchaudhri@egcrc.net
authors.forename: Nadia
authors.initials: N
authors.lastname: Chaudhri
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Caggiula
authors.forename: Eric C
authors.initials: EC
authors.lastname: Donny
authors.forename: Sheri
authors.initials: S
authors.lastname: Booth
authors.forename: Maysa A
authors.initials: MA
authors.lastname: Gharib
authors.forename: Laure A
authors.initials: LA
authors.lastname: Craven
authors.forename: Shannon S
authors.initials: SS
authors.lastname: Allen
authors.forename: Alan F
authors.initials: AF
authors.lastname: Sved
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Perkins
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D005260:Female; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D010775:Photic Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration; D012727:Sex Characteristics
chemical_list: D009538:Nicotine