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An essential role for ΔFosB in the nucleus accumbens in morphine action

Nature Neuroscience volume 9, pages 205–211 (2006)Cite this article

Abstract

The transcription factor ΔFosB is induced in the nucleus accumbens (NAc) and dorsal striatum by the repeated administration of drugs of abuse. Here, we investigated the role of ΔFosB in the NAc in behavioral responses to opiates. We achieved overexpression of ΔFosB by using a bitransgenic mouse line that inducibly expresses the protein in the NAc and dorsal striatum and by using viral-mediated gene transfer to specifically express the protein in the NAc. ΔFosB overexpression in the NAc increased the sensitivity of the mice to the rewarding effects of morphine and led to exacerbated physical dependence, but also reduced their sensitivity to the analgesic effects of morphine and led to faster development of analgesic tolerance. The opioid peptide dynorphin seemed to be one target through which ΔFosB produced this behavioral phenotype. Together, these experiments demonstrated that ΔFosB in the NAc, partly through the repression of dynorphin expression, mediates several major features of opiate addiction.

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Figure 1: ΔFosB in the NAc increases the sensitivity to morphine's rewarding effects.
Figure 2: ΔFosB in the NAc reduces morphine analgesia and accelerates morphine tolerance.
Figure 3: ΔFosB in the NAc exacerbates morphine physical withdrawal.
Figure 4: Repression of the dynorphin-encoding gene by ΔFosB in the NAc.
Figure 5: Administration of the κ opioid receptor antagonist nor-BNI in the NAc mimics the ΔFosB phenotype.

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Acknowledgements

This work was supported by grants from the National Institute on Drug Abuse and National Institute of Mental Health.

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Author notes

  1. Carlos A Bolanos

    Present address: Department of Psychology, Florida State University, Tallahassee, Florida, 32306-1270, USA

  2. Ralph J Dileone

    Present address: Department of Psychiatry, Yale University School of Medicine, 34 Park Street, New Haven, Connecticut, 06508, USA

Authors and Affiliations

  1. Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, 75390-9070, Texas, USA

    Venetia Zachariou, Carlos A Bolanos, David Theobald, Tamara Shaw-Lutchman, Olivier Berton, Ralph J Dileone, Arvind Kumar & Eric J Nestler

  2. Department of Basic Sciences, University of Crete, Faculty of Medicine, Heraklion, 71003, Crete, Greece

    Venetia Zachariou

  3. Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, 23298, Virginia, USA

    Dana E Selley, Michael P Cassidy & Laura J Sim-Selley

  4. Department of Anesthesia, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA

    Max B Kelz

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Correspondence to Eric J Nestler.

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Supplementary information

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Opioid Receptor Levels and Opiate Withdrawal Behaviors in Inducible Bitransgenic Mice (PDF 97 kb)

Supplementary Methods (PDF 82 kb)

Supplementary References (DOC 24 kb)

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Zachariou, V., Bolanos, C., Selley, D. et al. An essential role for ΔFosB in the nucleus accumbens in morphine action. Nat Neurosci 9, 205–211 (2006). https://doi.org/10.1038/nn1636

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