title: Cocaine self-administration behavior in inbred mouse lines segregating different capacities for inhibitory control.
abstract: BACKGROUND
  Various dimensions of impulsivity have been linked to substance abuse and dependence, both as consequences of, and as predisposing factors to addiction. With respect to the latter, they may be quantitative indicators of liability for substance use disorders (SUD) and aid in determining underlying genetic influences. We have previously determined that inhibitory control over impulsive responding, as measured by a reversal learning task, is heritable and under substantial genetic control, however their role as explaining variables for aspects of SUD have not been well explored.
  
  
  OBJECTIVE
  The aim of this study was to test for an association between genetically determined differences in inhibitory control and addiction-related phenotypes, such that phenotypes of poor inhibitory control would predict propensity for elevated operant drug-seeking and -taking behaviors.
  
  
  METHODS
  Mice from BxD strains with either good reversal learning (GRL) or poor reversal learning (PRL) ability were tested for intravenous cocaine self-administration under FR1, FR2, and FR5 reinforcement schedules. Additionally, locomotor responses to experimenter-delivered cocaine were assessed.
  
  
  RESULTS
  Compared to GRL strains, PRL strains acquired self-administration behavior more rapidly and administered cocaine at greater rates under all schedules of reinforcement, without any differences in discrimination index. In addition, PRL mice also exhibited increased responding during time-out periods. PRL strains also showed larger locomotor responses to 10 or 20 mg/kg injections of cocaine.
  
  
  CONCLUSIONS
  These studies demonstrate that heritable strain differences in inhibitory control do influence drug self-administration, thus suggest that genetically driven impulsivity of this type may predispose susceptibility to drug abuse and addiction.
authors.affiliation: Department of Psychology, University of California, P.O. Box 951563, Los Angeles, CA, 90095-1563, USA.
authors.forename: M Catalina
authors.initials: MC
authors.lastname: Cervantes
authors.forename: Rick E
authors.initials: RE
authors.lastname: Laughlin
authors.forename: J David
authors.initials: JD
authors.lastname: Jentsch
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000523:psychology*; D003216:Conditioning, Operant; D005260:Female; D007266:Inhibition, Psychological; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D012054:Reinforcement, Psychology; D012193:Reversal Learning / Q000187:drug effects*; D012646:Self Administration
chemical_list: D003042:Cocaine