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Determining the heritability of ethanol-induced locomotor sensitization in mice using short-term behavioral selection

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Abstract

Rationale

Sensitization to the locomotor stimulant effects of alcohol (ethanol) is thought to be a heritable risk factor for the development of alcoholism that reflects progressive increases in the positive motivational effects of this substance. However, very little is known about the degree to which genes influence this complex behavioral phenomenon.

Objectives

The primary goal of this work was to determine the heritability of ethanol-induced locomotor sensitization in mice using short-term behavioral selection.

Methods

Genetically heterogeneous C57BL/6J (B6) × DBA/2J (D2) F2 mice were generated from B6D2F1 progenitors, phenotyped for the expression of locomotor sensitization, and bred for high (HLS) and low (LLS) expression of this behavior. Selective breeding was conducted in two independently generated replicate sets to increase the confidence of our heritability estimates and for future correlated trait analyses.

Results

Large and significant differences in locomotor sensitization between HLS and LLS lines were evident by the fourth generation. Twenty-two percent of the observed line difference(s) were attributable to genes (h 2 = .22). Interestingly, locomotor activity in the absence of ethanol was genetically correlated with ethanol sensitization; high activity was associated with high sensitization.

Conclusions

That changes in ethanol sensitivity following repeated exposures are genetically regulated highlights the relevance of studies aimed at determining how genes regulate susceptibility to ethanol-induced behavioral and neural adaptations. As alcohol use and abuse disorders develop following many repeated alcohol exposures, these data emphasize the need for future studies determining the genetic basis by which changes in response to alcohol occur.

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Acknowledgments

This work was supported by NIAAA grant nos. AA015434 (SLB), AA016789 (SLB), and AA07462 (DNL). Special thanks to Heather Sissons for assistance with animal husbandry.

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Authors and Affiliations

  1. Psychobiology of Addictions, Department of Psychology and Indiana Alcohol Research Center, Indiana University–Purdue University Indianapolis, Indianapolis, IN, 46202, USA

    David N. Linsenbardt & Stephen L. Boehm II

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  1. David N. Linsenbardt
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  2. Stephen L. Boehm II
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Correspondence to David N. Linsenbardt.

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Linsenbardt, D.N., Boehm, S.L. Determining the heritability of ethanol-induced locomotor sensitization in mice using short-term behavioral selection. Psychopharmacology 230, 267–278 (2013). https://doi.org/10.1007/s00213-013-3151-4

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  • DOI: https://doi.org/10.1007/s00213-013-3151-4

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