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Mpdz is a quantitative trait gene for drug withdrawal seizures

Nature Neuroscience volume 7, pages 699–700 (2004)Cite this article

Abstract

Physiological dependence and associated withdrawal episodes can constitute a powerful motivational force that perpetuates drug use and abuse. Using robust behavioral models of drug physiological dependence in mice, positional cloning, and sequence and expression analyses, we identified an addiction-relevant quantitative trait gene, Mpdz. Our findings provide a framework to define the protein interactions and neural circuit by which this gene's product (multiple PDZ domain protein) affects drug dependence, withdrawal and relapse.

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Figure 1: Fine mapping of alcohol and pentobarbital withdrawal QTLs to a maximal 1.8-Mb interval, and analysis of 16 known and predicted genes in this interval.
Figure 2: MPDZ was more abundant in congenic than in background-strain mice.
Figure 3: Mpdz expression was genetically correlated with severities of withdrawal from alcohol and pentobarbital (PB) among standard inbred mouse strains.

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Acknowledgements

We thank J. Crabbe and J. Belknap for helpful discussions. Supported by US National Institutes on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism grants (RO1AA11114, RO1DA05228, P50AA10760, RO1AA06243 and F31AA13685).

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Author notes

  1. Renee L Shirley and Nicole A R Walter: These authors contributed equally to this work.

Authors and Affiliations

  1. Portland Alcohol Research Center and Department of Behavioral Neuroscience, and the Department of Veterans Affairs Medical Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, mailcode L-470, Portland, 97239-3098, Oregon, USA

    Renee L Shirley, Nicole A R Walter, Matthew T Reilly & Kari J Buck

  2. Department of Psychiatry, University of Mainz, Untere Zahlbacher Str. 8, Mainz, D-55131, Germany

    Christoph Fehr

Authors
  1. Renee L Shirley
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  2. Nicole A R Walter
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  3. Matthew T Reilly
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  4. Christoph Fehr
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  5. Kari J Buck
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Corresponding author

Correspondence to Kari J Buck.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Candidate gene primer sequences used for tissue expression panel (exp), sequencing (seq), and quantitative RT-PCR (RT-PCR). (PDF 93 kb)

Supplementary Methods (PDF 105 kb)

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Shirley, R., Walter, N., Reilly, M. et al. Mpdz is a quantitative trait gene for drug withdrawal seizures. Nat Neurosci 7, 699–700 (2004). https://doi.org/10.1038/nn1271

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