title: Effects of the combination of wheel running and atomoxetine on cue- and cocaine-primed reinstatement in rats selected for high or low impulsivity.
abstract: BACKGROUND
  Aerobic exercise and the attention-deficit/hyperactivity disorder medication, atomoxetine (ATO), are two monotherapies that have been shown to suppress reinstatement of cocaine-seeking in an animal model of relapse. The present study investigated the effects of combining wheel running and ATO versus each treatment alone on cocaine-seeking precipitated by cocaine and cocaine-paired cues in rats with differing susceptibility to drug abuse (i.e., high vs. low impulsive).
  
  
  METHODS
  Rats were screened for high (HiI) or low impulsivity (LoI) based on their performance on a delay-discounting task and then trained to self-administer cocaine (0.4 mg/kg/inf) for 10 days. Following 14 days of extinction, both groups were tested for reinstatement of cocaine-seeking precipitated by cocaine or cocaine-paired cues in the presence of concurrent running wheel access (W), pretreatment with ATO, or both (W+ATO).
  
  
  RESULTS
  HiI rats acquired cocaine self-administration more quickly than LoI rats. While both individual treatments and W+ATO significantly attenuated cue-induced cocaine seeking in HiI and LoI rats, only W+ATO was effective in reducing cocaine-induced reinstatement compared with vehicle treatment. There were dose-dependent and phenotype-specific effects of ATO with HiI rats responsive to the low but not high ATO dose. Floor effects of ATO and W on cue-induced reinstatement prevented the assessment of combined treatment effects.
  
  
  CONCLUSIONS
  These findings demonstrated greater attenuation of cue- versus cocaine-induced reinstatement by ATO and W alone and recapitulate impulsivity phenotype differences in both acquisition of cocaine self-administration and receptivity to treatment.
authors.affiliation: Graduate Program in Neuroscience, University of Minnesota Medical School, Jackson Hall, 321 Church St. SE, Minneapolis, MN, 55455, USA, zleb0002@umn.edu.
authors.forename: Natalie E
authors.initials: NE
authors.lastname: Zlebnik
authors.forename: Marilyn E
authors.initials: ME
authors.lastname: Carroll
mesh_terms: D000818:Animals; D000069445:Atomoxetine Hydrochloride; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders; D003463:Cues; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D005260:Female; D007175:Impulsive Behavior / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D010805:Physical Conditioning, Animal; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012420:Running; D012646:Self Administration
chemical_list: D011437:Propylamines; D000069445:Atomoxetine Hydrochloride; D003042:Cocaine