title: Sex differences in the effect of wheel running on subsequent nicotine-seeking in a rat adolescent-onset self-administration model.
abstract: BACKGROUND
  Wheel running attenuates nicotine-seeking in male adolescent rats; however, it is not known if this effect extends to females.
  
  
  OBJECTIVE
  To determine if wheel running during abstinence would differentially attenuate subsequent nicotine-seeking in male and female rats that had extended access to nicotine self-administration during adolescence.
  
  
  METHODS
  Male (n = 49) and female (n = 43) adolescent rats self-administered saline or nicotine (5 μg/kg) under an extended access (23-h) paradigm. Following the last self-administration session, rats were moved to polycarbonate cages for an abstinence period where they either had access to a locked or unlocked running wheel for 2 h/day. Subsequently, nicotine-seeking was examined under a within-session extinction/cue-induced reinstatement paradigm. Due to low levels of nicotine-seeking in females in both wheel groups, additional groups were included that were housed without access to a running wheel during abstinence.
  
  
  RESULTS
  Females self-administered more nicotine as compared to males; however, within males and females, intake did not differ between groups prior to wheel assignment. Compared to saline controls, males and females that self-administered nicotine showed a significant increase in drug-seeking during extinction. Wheel running during abstinence attenuated nicotine-seeking during extinction in males. In females, access to either locked or unlocked wheels attenuated nicotine-seeking during extinction. While responding was reinstated by cues in both males and females, levels were modest and not significantly affected by exercise in this adolescent-onset model.
  
  
  CONCLUSIONS
  While wheel running reduced subsequent nicotine-seeking in males, access to a wheel, either locked or unlocked, was sufficient to suppress nicotine-seeking in females.
authors.affiliation: Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, 1670 Discovery Drive, Suite 110, Charlottesville, VA, 22911, USA.
authors.forename: Victoria
authors.initials: V
authors.lastname: Sanchez
authors.forename: Catherine F
authors.initials: CF
authors.lastname: Moore
authors.forename: Darlene H
authors.initials: DH
authors.lastname: Brunzell
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Lynch
mesh_terms: D000818:Animals; D058999:Drug-Seeking Behavior / Q000187:drug effects* / Q000502:physiology; D005108:Extinction, Psychological / Q000502:physiology; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D012420:Running / Q000502:physiology; D012646:Self Administration; D012727:Sex Characteristics; D013997:Time Factors
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine