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

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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.