Expression of the transcription factor ΔFosB in the brain controls sensitivity to cocaine

Max B. Kelz, Jingshan Chen, William A. Carlezon, Kim Whisler, Lauren Gilden, Alison M. Beckmann, Cathy Steffen, Ya Jun Zhang, Louis Marotti, David W. Self, Tatiana Tkatch, Gytis Baranauskas, D. James Surmeler, Rachael L. Neve, Ronald S. Duman, Marina R. Picciotto, Eric J. Nestler

Research output: Contribution to journalArticlepeer-review

497 Scopus citations

Abstract

Acute exposure to cocaine transiently induces several Fos family transcription factors in the nucleus accumbens, a region of the brain that is important for addiction. In contrast, chronic exposure to cocaine does not induce these proteins, but instead causes the persistent expression of highly stable isoforms of ΔFosB. ΔFosB is also induced in the nucleus accumbens by repeated exposure to other drugs of abuse, including amphetamine, morphine, nicotine and phencyclidine. The sustained accumulation of ΔFosB in the nucleus accumbens indicates that this transcription factor may mediate some of the persistent neural and behavioural plasticity that accompanies chronic drug exposure. Using transgenic mice in which ΔFosB can be induced in adults in the subset of nucleus accumbens neurons in which cocaine induces the protein, we show that ΔFosB expression increases the responsiveness of an animal to the rewarding and locomotor-activating effects of cocaine. These effects of ΔFosB appear to be mediated partly by induction of the AMPA (α- amino-3-hydroxy-5-methyl-4-isoxazole) glutamate receptor subunit GluR2 in the nucleus accumbens. These results support a model in which ΔFosB, by altering gene expression, enhances sensitivity to cocaine and may thereby contribute to cocaine addiction.

Original languageEnglish (US)
Pages (from-to)272-276
Number of pages5
JournalNature
Volume401
Issue number6750
DOIs
StatePublished - Sep 16 1999

ASJC Scopus subject areas

  • General

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