Cocaine and amphetamine-regulated transcript (CART) peptides are neurotransmitters with important roles in drug abuse. The increase of CART expression in the brain induced by psychostimulants is associated with changes of behavior in addicted animals. We expressed and purified the single-chain variable fragments antibody (scFv) against CART55-102, and observed the effect of CART scFv on the expression of cocaine-induced behavior sensitization in mice. Results showed that the titer of CART scFv was 1.6 μg/ml. Single administration of CART scFv (intraperitoneal 0.04, 0.2, and 1 mg/kg) reduced the increasing locomotor activity induced by chronic cocaine intake in mice (P<0.05-0.01), but failed to affect the locomotor activity of naive mice. These results suggested that CART scFv may be a potential therapeutic tool to treat drug abuse.