expression of immediate-early genes such as Jun and Fos, which encode transcription factors. The transcripts of these gene return to control levels, and following repeated administration of the drugs, desentization is seen (Hope, Kosofsky, Hyman, & Nestler, 1992). The transcription factors FosB (Hope et al., 1992; Nestler, 2008) and CREB (Carlezon, Duman, & Nestler, 2005) have also been well documented as key components targeted by multiple signal transduction pathways and are involved in regulating expression of drug response genes. Binding of the Fos/Jun heterodimer to AP-1 sites and CREB to cAMP-response elements (CREs) in gene promoters activates transcription of the targeted genes. Another group of well-studied immediate-early gene products is the Nur transcription factors that bind to Nur-responsive elements. These are widely present in the hypothalamus–pituitary–adrenal axis and show rapid and transient increases in expression during acute exposure to addictive drugs (Campos-Melo, Galleguillos, Sanchez, Gysling, & Andres, 2013).
