We next tested directly whether elevated sirtuin activity in the NAc is involved in behavioral responses to cocaine. To do this, we used resveratrol and sirtinol in the conditioned place preference assay, where animals learn to prefer a cocaine-paired environment. We administered resveratrol systemically since this drug is known to penetrate the brain after systemic administration (Baur and Sinclair, 2006), and sirtinol directly into the NAc using an osmotic minipump connected to guide cannulae. Similar to our electrophysiological observations, resveratrol and sirtinol exerted opposite effects on cocaine reward, with resveratrol significantly enhancing cocaine place conditioning and sirtinol significantly attenuating it (Figs. 5A, 5B).
