A number of studies has shown that signaling through the cAMP response element binding protein (CREB)-mediated pathway is utilized by various forms of reinforcing stimuli, including drugs of abuse (Carlezon et al., 1998; Nestler, 2001) and non-drug stimuli (Jin et al., 2005). Both cocaine and amphetamine can activate the CREB transcriptional machinery via increased CREB phosphorylation (Carlezon et al., 2005), leading to altered expression patterns of several transcription factors downstream of CREB, such as c-fos, zif268, and fosB (Harlan and Garcia, 1998; McGinty et al., 2008), and altered mRNA splicing of Fos family members that enable accumulation of ΔFosB (McClung et al., 2004). Here, we will review CREB-related signaling mechanisms that can interface with AMPA receptor plasticity and perhaps modulate responding for drugs of abuse.
