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Two well-known appetite-regulatory peptides, leptin and cocaine- and amphetamine-regulated transcript (CART), are known to be involved in the brain rewarding pathway. However, it is not yet known how they interact in the nucleus accumbens, an important region mediating the rewarding effects of drugs of abuse. Using the immunoassay method, we found that a microinjection of leptin into the nucleus accumbens core induces an immediate and transient increase of the CART peptide in this site, whereas these effects were inhibited by cocaine. These results expand the role of accumbal leptin to the regulation of the CART peptide and further suggest that possible interaction of these appetite-regulating peptides may be involved in cocaine-mediated rewarding effects.