cocaine, amphetamine, and D1 agonists [53, 54, 76, 77]. Conversely, overexpression of the Class II HDACs, HDAC4 or HDAC5 (but not HDAC9), in the NAc significantly attenuates cocaine reward [53, 54], but it is not yet known if HDAC4/5 overexpression also reduces the locomotor-activating effects of cocaine. The behavioral effects of HDAC overexpression in the NAc likely require histone deacetylation, since deletion of the catalytic deacetylase domain of HDAC5 prevents its inhibitory effects on cocaine reward [54]. However, since HDAC5 also interacts with HDAC3 at this same domain [78], it is unclear whether HDAC5’s effects on cocaine reward are due to its own catalytic activity or its interaction with HDAC3.
