The role played by the biologically active CART 55–102 peptide in NAcc AMPH induced locomotion was investigated. When microinjected alone into this site, none of the doses of CART 55–102 tested (0.1, 0.4, 1.0 or 2.5 μg/0.5 μl/side) produced effects on locomotion during a two-h test. However, when co-injected with AMPH (2.5 μg/0.5 μl/side) into the NAcc, moderately high (2.5 μg/side) and middle to high (0.4–2.5 μg/side) doses of CART 55–102 significantly attenuated the effects of AMPH on locomotion and rearing, respectively. These results indicate that CART peptides can exert an antagonistic effect on the generation of locomotion by AMPH in the NAcc.