As discussed above, HATs are enzymes which catalyze the addition of acetyl groups onto histone proteins. One of the best studied HATs is CBP, which is known to associate with phosphorylated CREB and assist in target gene activation [36, 69]. While cocaine increases H4 acetylation on the fosb promoter in striatum of wild type mice, this does not occur in CBP-deficient mice [34]. Moreover, this cocaine-induced acetylation event on fosb and perhaps other genes may be behaviorally important, as CBP-deficient mice are also less sensitive to the locomotor-activating effects of cocaine. These findings suggest that CBP is an important HAT in mediating at least some of the cocaine-induced increases in histone acetylation and ultimately the downstream behavioral responses [34]. The reduced sensitivity of CBP-deficient mice to cocaine may be independent of CREB, since other manipulations which reduce CREB activity in striatum typically enhance behavioral responses to cocaine [70, 71]. However, since CBP-deficient mice have reduced CBP levels in all brain regions throughout development, it will be important to determine which specific regions in the adult brain are important for CBP’s
