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Selective Breeding for Divergence in Novelty-seeking Traits: Heritability and Enrichment in Spontaneous Anxiety-related Behaviors

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Outbred Sprague–Dawley rats can be classified as high responders (HR) or low responders (LR) based on their levels of exploratory locomotion in a novel environment. While this novelty-seeking dimension was originally related to differential vulnerability to substance abuse, behavioral, neuroendocrine and gene expression studies suggest a fundamental difference in emotional reactivity between these animals. Here, we report the first study to selectively breed rats based on this novelty-seeking dimension. Response to novelty was clearly heritable, with a >2-fold difference in behavior seen after eight generations of selection. Three tests of anxiety-like behavior consistently showed significantly greater anxiety in LR-bred rats compared to HR-bred animals, and this difference was diminished in the open field test by administration of the anxiolytic benzodiazepine drug, chlordiazepoxide. Cross-fostering revealed that responses to novelty were largely unaffected by maternal interactions, though there was an effect on anxiety-like behavior. These selected lines will enable future research on the interplay of genetic, environmental and developmental variables in controlling drug seeking behavior, stress and emotional reactivity.

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ACKNOWLEDGEMENTS

We are grateful to Jim Stewart, Keith Vasquez, Ceylan Isgor, Xin-Yun Lu and Andrew Osetek for technical assistance. This study was funded by the Office of Naval Research, grant N00014-02-1-0879 to HA, NIDA RO1 DA13386 to HA and NIMH PO1 MH42251 to SJW.

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Authors and Affiliations

  1. Institute for Neuroscience, Carleton University, Ottawa, Ont., K1S 5B6, Canada

    John D. H. Stead

  2. Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, 48109-0720, USA

    Sarah Clinton, Johanna Schneider, Abas Jama, Sue Miller, Delia M. Vazquez, Stanley J. Watson & Huda Akil

  3. Department of Pediatrics & Neonatology, University of Hawaii, Honolulu, Hawaii, 96826, USA

    Charles Neal

  4. Department of Psychology, Institute for Neuroscience, Carleton University, 513A Loeb Building, 1125 Colonel By Drive, Ottawa, Ont., K1S 5B6, Canada

    John D. H. Stead

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  1. John D. H. Stead
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  2. Sarah Clinton
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  3. Charles Neal
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  4. Johanna Schneider
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  7. Delia M. Vazquez
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  9. Huda Akil
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Correspondence to John D. H. Stead.

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John H. Stead and Sarah Clinton contributed equally to this research.

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Stead, J.D.H., Clinton, S., Neal, C. et al. Selective Breeding for Divergence in Novelty-seeking Traits: Heritability and Enrichment in Spontaneous Anxiety-related Behaviors. Behav Genet 36, 697–712 (2006). https://doi.org/10.1007/s10519-006-9058-7

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  • DOI: https://doi.org/10.1007/s10519-006-9058-7

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