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A verification of previously identified QTLs for cocaine-induced activation using a panel of B6.A chromosome substitution strains (CSS) and A/J x C57Bl/6J F2 mice

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Abstract

Background

The objective of this study was to confirm provisional quantitative trait loci (QTL) for cocaine-induced locomotor activation, on chromosomes 1, 5, 6, 9, 12, 15, 16, 17, and 18, previously identified in the AXB/BXA recombinant inbred (RI) and AcB/BcA recombinant congenic (RC) strains of mice derived from A/J (A) and C57BL/6J (B6) progenitors. This was accomplished through a genetic analysis of cocaine-induced activity in an AxB6 F2 cross and a phenotypic survey across a panel of B6.A chromosome substitution strains (CSS) mice. Mice were tested for cocaine-induced activity, following administration of saline and cocaine (20 mg/kg), utilizing an open-field procedure.

Results

Among AxB6 F2 mice, differences in cocaine-induced activity were associated with loci on chromosome 1 (D1Mit305), 5 (D5Mit409), 16 (D16Mit131), and 18 (D18Mit189). A survey of the CSS panel confirmed cocaine QTLs on chromosomes 5 and 15, previously identified in RI or RC strains. Overall, the regions on chromosomes 5 and 18 represent verification of QTL previously identified in both the RC and RI strains. Additionally, the B6 allele for these QTL was consistently associated with greater relative cocaine activation.

Conclusions

Collectively, chromosome 5 and 18 QTL have now been replicated in multiple independent crosses derived from the A/J and C57BL/6J progenitors. The use of an in silico analysis highlighted potential candidate genes on chromosomes 5 and 18. The present results complement the targeted gene approach currently prevalent in the study of cocaine and provide a broader empirically based focus for subsequent candidate gene studies.

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Acknowledgment

This research was supported by funds awarded to K.G. from the Canadian Institutes of Health Research (CIHR).

Conflicts of interest

Drs. Alan Boyle and Kathryn Gill report that they have no conflicts of interest as related to the present manuscript. Additionally, the present authors do not have any additional financial support, compensation, or personal financial holdings to disclose according to journal policy.

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Authors and Affiliations

  1. Department of Psychiatry, Research Institute, McGill University Health Centre, R3-117, 1650 Cedar Avenue, Montreal, H3G 1A4, Canada

    Alan E. Boyle

  2. Addictions Unit, McGill University Health Centre, 1547 Pine Avenue West, Montreal, H3G 1B3, Canada

    Kathryn J. Gill

  3. Department of Psychiatry, McGill University, Montreal, QC, Canada

    Kathryn J. Gill

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  1. Alan E. Boyle
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  2. Kathryn J. Gill
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Correspondence to Kathryn J. Gill.

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Boyle, A.E., Gill, K.J. A verification of previously identified QTLs for cocaine-induced activation using a panel of B6.A chromosome substitution strains (CSS) and A/J x C57Bl/6J F2 mice. Psychopharmacology 207, 325–334 (2009). https://doi.org/10.1007/s00213-009-1656-7

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  • DOI: https://doi.org/10.1007/s00213-009-1656-7

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