Small molecule inhibitors of HDACs have been used in many systems since they were first identified in 1978 [73], but have only recently been used to study behavior. Sodium butyrate, a highly non-specific HDAC inhibitor, was the first discovered [73], followed by more specific and potent inhibitors trichostatin A (TSA) [74], a fungal antibiotic, and suberoylanilide hydroxamic acid (SAHA) [75], which is currently FDA-approved for treatment of cutaneous T-cell lymophoma. Recent studies have shown that each of these HDAC inhibitors potentiates the locomotor-activating effects of psychostimulants, as measured by the number of horizontal infrared beam breaks, as well as the rewarding effects psychostimulants, as measured by conditioned place preference [53, 54, 76]. Importantly, systemic administration of sodium butyrate or TSA, or the direct infusion of SAHA into the NAc, is sufficient to potentiate the locomotor activating or rewarding effects of 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
