DeltaFosB: A Molecular Switch for Reward (2013)

Journal of Drug and Alcohol Research

vol. 2 (2013), Article ID 235651, 11 pages

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doi:10.4303/jdar/235651

Eric J. Nestler

Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1065, New York, NY 10029, USA

Received 2 November 2012; Revised 10 November 2012; Accepted 20 November 2012

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ΔFosB is a member of the Fos family of transcription factors. While all other family members are induced rapidly but transiently in response to a host of acute stimuli, ΔFosB is unique in that it accumulates in response to repeated stimulation due to its unusual protein stability.

Such a prolonged induction of ΔFosB, within the brain’s reward regions, has been implicated in animal models of drug addiction, with a wealth of evidence indicating that ΔFosB promotes reward and motivation and serves as a key mechanism of drug sensitization and increased drug self-administration. This has been validated in humans postmortem, with elevated ΔFosB levels seen in reward regions of the addicted brain.

As a transcription factor, ΔFosB produces this behavioral phenotype by regulating the expression of specific target genes. We are identifying such transcriptional targets of ΔFosB by use of a candidate gene approach as well as by use of genome-wide methods. Recent work has analyzed chromatin remodeling—changes in the posttranslational modifications of histones and other nuclear proteins at drug-regulated genes—to delineate the detailed molecular mechanisms by which ΔFosB regulates target gene expression in vivo to mediate drug-induced synaptic, neural, and behavioral plasticity. These studies of ΔFosB are providing new insight into the molecular basis of drug addiction, which is defining a host of new targets for possible therapeutic development.

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DeltaFosB: Ibaba Kan ti Yi pada fun Ere (2013)

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