Enhanced acquisition of cocaine self-administration by increasing percentages of C57BL/6J genes in mice with a nonpreferring outbred background

Eduardo Ruiz-Durántez, Stephanie K. Hall, Cathy Steffen, David W. Self

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Rationale: Individual differences in the propensity to acquire drug self-administration may have a substantial genetic basis. Objectives: To study the genetic contribution to cocaine self-administration by comparing hybrids of cocaine preferring (C57BL/6J) and nonpreferring (ICR) mice. Methods: ICR and C57BL/6J parental strains were compared to hybrids with 75% ICR:25% C57BL/6J, 50% ICR:50% C57BL/6J, and 25% ICR:75% C57BL/6J genetic backgrounds for acquisition of sucrose pellet and intravenous cocaine self-administration in 1-h test sessions. Mice that acquired cocaine self-administration were subsequently tested in a between-session self-administration dose-response procedure. Results: Increasing presence of C57BL/6J genes increased the percentage of mice that acquired sucrose pellet self-administration in the first test session. In lever-trained mice, only 19% of ICR mice met acquisition criteria for cocaine self-administration after 15 sessions, whereas 76% of C57BL/6J mice met acquisition criteria, although both strains initially sampled a similar number of cocaine injections. Increasing the percentage of C57BL/6J genes in the nonpreferring ICR background to 50 and 75% led to increasing percentages of mice that met acquisition criteria to 31 and 52%, respectively. In mice that acquired self-administration, only mice with 75% C57BL/6J genes showed a typical inverted U-shaped self-administration dose-response curve, whereas the curve was flat across doses for mice with ≤50 and 100% C57BL/6J genes. Conclusions: The findings are consistent with a genetically based dose-dependent enhancement of cocaine reinforcement by C57BL/6J genes. These results suggest that heritable traits impart a substantial genetic load that facilitates the propensity for cocaine addiction among individuals in outbred populations.

Original languageEnglish (US)
Pages (from-to)553-560
Number of pages8
Issue number4
StatePublished - Jul 2006


  • Addiction
  • Hybrid mouse strains
  • ICR mice
  • Reinforcement

ASJC Scopus subject areas

  • Pharmacology


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