Leptin in the rat’s nucleus accumbens (NAcc) core has previously shown to disrupt the effects of acute administration of cocaine on both locomotor activity and the phosphorylation levels of glycogen synthase kinase 3β. In the present study, we further measured the phosphorylation levels of GluA1 after bilateral microinjections of leptin in this site followed by acute administration of cocaine. Interestingly, leptin in the NAcc core significantly blocks the increase of GluA1 phosphorylation levels at serine 845 induced by acute administration of cocaine. These effects were not observed for GluA1 phosphorylation levels at serine 831. We have also found additional evidence that glycogen synthase kinase 3β may play a major role in mediating these processes.