title: Cocaine-, caffeine-, and stress-evoked cocaine reinstatement in high vs. low impulsive rats: treatment with allopregnanolone.
abstract: BACKGROUND
  Previous research indicates that individual differences in traits such as impulsivity, avidity for sweets, and novelty reactivity are predictors of several aspects of drug addiction. Specifically, rats that rank high on these behavioral measures are more likely than their low drug-seeking counterparts to exhibit several characteristics of drug-seeking behavior. In contrast, initial work suggests that the low drug-seeking animals are more reactive to negative events (e.g., punishment and anxiogenic stimuli). The goal of this study was to compare high and low impulsive rats on reinstatement of cocaine-seeking behavior elicited by cocaine (COC) and by negative stimuli such as the stress-inducing agent yohimbine (YOH) or a high dose of caffeine (CAFF). An additional goal was to determine whether treatment with allopregnanolone (ALLO) would reduce reinstatement (or relapse) of cocaine-seeking behavior under these priming conditions.
  
  
  METHODS
  Female rats were selected as high (HiI) or low (LoI) impulsive using a delay-discounting task. After selection, they were allowed to self-administer cocaine for 12 days. Cocaine was then replaced with saline, and rats extinguished lever responding over 16 days. Subsequently, rats were pretreated with either vehicle control or ALLO, and cocaine seeking was reinstated by injections of COC, CAFF, or YOH.
  
  
  RESULTS
  While there were no phenotype differences in maintenance and extinction of cocaine self-administration or reinstatement under control treatment conditions, ALLO attenuated COC- and CAFF-primed reinstatement in LoI but not HiI rats.
  
  
  CONCLUSIONS
  Overall, the present findings suggest that individual differences in impulsive behavior may influence efficacy of interventions aimed to reduce drug-seeking behavior.
authors: Graduate Program in Neuroscience, University of Minnesota, Minneapolis, MN 55455, United States. Electronic address: regi0011@umn.edu.
authors: Paul S
authors: PS
authors: Regier
authors: Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455, United States.
authors: Alexander B
authors: AB
authors: Claxton
authors: Graduate Program in Neuroscience, University of Minnesota, Minneapolis, MN 55455, United States; Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455, United States.
authors: Natalie E
authors: NE
authors: Zlebnik
authors: Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455, United States.
authors: Marilyn E
authors: ME
authors: Carroll
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage* / Q000009:adverse effects*; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D003216:Conditioning, Operant / Q000187:drug effects; D065786:Delay Discounting / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D005260:Female; D007175:Impulsive Behavior / Q000502:physiology*; D011280:Pregnanolone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012008:Recurrence; D012646:Self Administration; D015016:Yohimbine / Q000494:pharmacology*
chemical_list: D015016:Yohimbine; D002110:Caffeine; D011280:Pregnanolone; D003042:Cocaine
keywords: Allopregnanolone; Caffeine; Cocaine; Impulsivity; Reinstatement; Self-administration; Yohimbine