Another downstream CREB target, ΔFosB, is also quite interesting, in part due to a unique, accumulating expression pattern in DA terminal fields of the mesocorticolimbic circuit following repeated administration of commonly abused drugs, including cocaine and amphetamine, as well as following repeated, non-drug reinforcement (McClung et al., 2004; McClung and Nestler, 2003). ΔFosB is a transcription factor that acts to upregulate GluA2 in the NAcb (Kelz et al., 1999) and cyclin-dependent kinase 5 (Cdk5) in the striatal complex (Bibb et al., 2001) and hippocampus (Chen et al., 2000). Overexpression of GluA2 in the NAcb shell decreases intracranial self-stimulation thresholds (Todtenkopf et al., 2006), suggesting that ΔFosB accumulation might augment drug-mediated reinforcement. It has been shown that ΔFosB overexpression increases the incentive motivation to seek both drug and non-drug reinforcement, while ΔFosB dominant-negative overexpression reduces motivation to seek these reinforcers (Colby et al., 2003; Nestler, 2005).
