A. Systemic administration of the sirtuin agonist, resveratrol (20 mg/kg ip, dissolved in 5% hydroxypropyl β-cyclodextrin vehicle), increases the rewarding effects of cocaine (5 mg/kg) in the conditioned place preference paradigm (p < 0.05, n = 9–12). B. Intra-NAc delivery of the sirtuin antagonist, sirtinol (50 μM in 5% hydroxypropyl β-cyclodextrin), decreases the rewarding effects of 10 mg/kg cocaine (right). Data are expressed as mean ± s.e.m. (n = 9–12 in each group), *p < 0.05 by t-test. C. Intra-NAc delivery of sirtinol (100 μM) in rats that were trained to self-administer cocaine significantly reduced the number of cocaine infusions at the threshold dose of 62 μg/infusion (*p < 0.05, n = 5–7). D. The sirtinol-induced decrease in cocaine self-administration was specific to the active (cocaine-associated) nose poke apertures, as they behaved normally at the inactive apertures. E. Sirtinol significantly reduces ERK1/2 phosphorylation under depolarizing conditions in acute NAc slices ex vivo (*p < 0.05, n = 4).