Expression of the transcription factor Delta FosB in the brain controls sensitivity to cocaine

Acute exposure to cocaine transiently induces several Fos family transcript ion factors in the nucleus accumbens(1), a region of the brain that is impo rtant for addiction(2,3). In contrast, chronic exposure to cocaine does not induce these proteins, but instead causes the persistent expression of hig hly stable isoforms of Delta FosB(4-6). Delta FoSB is also induced in the n ucleus accumbens by repeated exposure to other drugs of abuse, including am phetamine, morphine, nicotine and phencyclidine(7-10). The sustained accumu lation of Delta FosB in the nucleus accumbens indicates that this transcrip tion factor may mediate some of the persistent neural and behavioural plast icity that accompanies chronic drug exposure(1). Using transgenic mice in w hich Delta FosB can be induced in adults in the subset of nucleus accumbens neurons in which cocaine induces the protein,we show that Delta FosB expre ssion increases the responsiveness of an animal to the rewarding and locomo tor-activating effects of cocaine. These effects of Delta FosB appear to be mediated partly by induction of the AMPA (alpha-amino-3-hydroxy-5-methyl-4 -isoxazole) glutamate receptor subunit GluR2 in the nucleus accumbens. Thes e results support a model in which Delta FosB, by altering gene expression, enhances sensitivity to cocaine and may thereby contribute to cocaine addi ction.