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Utility of genetically modified mice for understanding the neurobiology of substance use disorders

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Abstract

Advances in our ability to modify the mouse genome have enhanced our understanding of the genetic and neurobiological mechanisms contributing to addiction-related behaviors underlying substance use and abuse. These experimentally induced manipulations permit greater spatial and temporal specificity for modification of gene expression within specific cellular populations and during select developmental time periods. In this review, we consider the current mouse genetic model systems that have been employed to understand aspects of addiction and highlight significant conceptual advances achieved related to substance use and abuse. The mouse models reviewed herein include conventional knockout and knockin, conditional knockout, transgenic, inducible transgenic, mice suitable for optogenetic control of discrete neuronal populations, and phenotype-selected mice. By establishing a reciprocal investigatory relationship between genetic findings in humans and genomic manipulations in mice, a far better understanding of the discrete neuromechanisms underlying addiction can be achieved, which is likely to provide a strong foundation for developing and validating novel therapeutics for the treatment of substance abuse disorders.

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Acknowledgment

Supported by the National Institute on Drug Abuse (DA020686 to PJK; DA026693 to CDF).

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  1. Laboratory of Behavioral and Molecular Neuroscience, Department of Molecular Therapeutics, The Scripps Research Institute, Scripps, Florida, Jupiter, FL, 33458, USA

    Christie D. Fowler & Paul J. Kenny

  2. Laboratory of Behavioral and Molecular Neuroscience, Department of Neuroscience, The Scripps Research Institute, Scripps, Florida, Jupiter, FL, 33458, USA

    Christie D. Fowler & Paul J. Kenny

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Fowler, C.D., Kenny, P.J. Utility of genetically modified mice for understanding the neurobiology of substance use disorders. Hum Genet 131, 941–957 (2012). https://doi.org/10.1007/s00439-011-1129-z

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