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An essential role for DeltaFosB in the nucleus accumbens in morphine action. Nat Neurosci 9:205-211

Department of Psychiatry and Center for Basic Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9070, USA.
Nature Neuroscience (Impact Factor: 14.98). 03/2006; 9(2):205-11. DOI: 10.1038/nn1636
Source: PubMed

ABSTRACT The transcription factor DeltaFosB is induced in the nucleus accumbens (NAc) and dorsal striatum by the repeated administration of drugs of abuse. Here, we investigated the role of DeltaFosB in the NAc in behavioral responses to opiates. We achieved overexpression of DeltaFosB 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. DeltaFosB 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 DeltaFosB produced this behavioral phenotype. Together, these experiments demonstrated that DeltaFosB in the NAc, partly through the repression of dynorphin expression, mediates several major features of opiate addiction.

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    • "Regulation of PDYN gene expression is a complex phenomenon that may implicate several transcription factors including avian myelocytomatosis viral oncogene homolog (c-Myc), neuron restrictive silencer factor (NRSF)/RE1-silencing transcription factor (REST) [36] [52] [53], USF1/2, AP-1 family protein, FBJ murine osteosarcoma viral oncogene homolog B (FosB), cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), downstream regulatory element (DRE) antagonist modulator (DREAM), yin-yang1 (YY1) and NF-kB [54] [55] [56] [57]. c-Myc may directly interact with its binding motif in PDYN gene to regulate its function while AP-1 may either interact directly or recruit other proteins to regulate PDYN expression. "
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    • "For instance, repeated morphine injections produce a marked decrease in brain μ-opioid receptor (MOP receptor) density (Davis et al., 1979; Tao et al., 1987; Diaz et al., 2000), down-regulation of the high-affinity MOP receptor site in rats and reduction of MOP receptor signalling in sensory neurons and brainstem nuclei (Sim et al., 1996; Johnson et al., 2006). Changes in transcription factor activation following chronic opioid treatment have also been proposed to play a relevant role in opioid tolerance and addiction (Carlezon et al., 2005; Zachariou et al., 2006). "
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