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

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Abstract

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.

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Acknowledgements

This work was supported by United States Public Health Service Grants DA 10460, DA 08227, a fellowship from the Basque Government (E. R-D.), and the Wesley Gilliland Professorship in Biomedical Research.

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Authors and Affiliations

  1. Department of Psychiatry, The Seay Center for Basic and Applied Research in Psychiatric Illness, UT Southwestern Medical Center, Dallas, TX, 75390-9070, USA

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

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  1. Eduardo Ruiz-Durántez
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  2. Stephanie K. Hall
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  3. Cathy Steffen
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  4. David W. Self
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Correspondence to David W. Self.

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Ruiz-Durántez, E., Hall, S.K., Steffen, C. et al. Enhanced acquisition of cocaine self-administration by increasing percentages of C57BL/6J genes in mice with a nonpreferring outbred background. Psychopharmacology 186, 553–560 (2006). https://doi.org/10.1007/s00213-006-0379-2

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  • DOI: https://doi.org/10.1007/s00213-006-0379-2

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