title: Cocaine self-administration under fixed and progressive ratio schedules of reinforcement: comparison of C57BL/6J, 129X1/SvJ, and 129S6/SvEvTac inbred mice.
abstract: BACKGROUND
  Combining strains to generate mutant mice may obscure conclusions regarding the targeted gene. Specifically, cocaine may have reduced reinforcing effects in 129 substrains compared to the C57BL/6 strain, commonly used for ES cells and breeding, respectively.
  
  
  OBJECTIVE
  We tested the hypothesis that reinforcing effects of cocaine differ between the C57BL/6J strain and two substrains of 129, 129X1/SvJ and 129S6/SvEvTac.
  
  
  METHODS
  To assess and reduce performance differences, operant responding was established with liquid food as a reinforcer and evaluated under fixed and progressive ratio schedules. Dose-effect functions for intravenous cocaine self-administration were then determined under both schedules. Finally, reinforced and nonreinforced manipulanda were reversed to assess acquisition of self-administration using a previously nonreinforced response.
  
  
  RESULTS
  Relative to C57BL/6J mice, 129X1/SvJ mice showed decreased reinforcing effects of low-magnitude food and cocaine reinforcers. Dose-effect functions for cocaine self-administration were comparable between C57BL/6J and 129S6/SvEvTac mice, despite delayed acquisition of operant behaviors and rightward shifts in the food concentration-effect functions in 129S6/SvEvTac mice. A high cocaine dose clearly served as a positive reinforcer in all three strains in a reversal procedure.
  
  
  CONCLUSIONS
  Relative to C57BL/6J mice, the reinforcing effects of cocaine were diminished in 129X1/SvJ mice, but only for low cocaine doses, and a similar profile was observed with food reinforcement. 129S6/SvEvTac mice required more extensive operant training than C57BL/6J mice did, but after acquisition, reinforcing effects of cocaine were similar in the two strains. We suggest that comparable phenotypes observed in gene-targeting studies may result from genetic background, whereas more profound or qualitatively different phenotypes may be more confidently attributed to targeted mutations.
authors.affiliation: Alcohol and Drug Abuse Research Center, McLean Hospital-Harvard Medical School, 115 Mill Street, Belmont, MA, 02478, USA.
authors.forename: Morgane
authors.initials: M
authors.lastname: Thomsen
authors.forename: S Barak
authors.initials: SB
authors.lastname: Caine
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019970:Cocaine-Related Disorders / Q000523:psychology*; D003216:Conditioning, Operant / Q000187:drug effects*; D005502:Food; D006262:Health; D007262:Infusions, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration; D013045:Species Specificity