Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide found throughout the brain, particularly in the nucleus accumbens (NAcc) and hypothalamus. CART was initially discovered and named based on the upregulation of its mRNA in the striatum after acute cocaine or amphetamine injection in rats. CART is also known to participate in a wider range of physiological functions including feeding, anxiety, bone resorption, and insulin regulation. In this report, we demonstrate that knockout mice lacking a functional CART gene show similar cocaine-induced locomotor sensitization and cocaine self-administration to their wild type siblings. Intravenous cocaine self-administration did not differ between CART wild type and knockout mice during acquisition, during schedules of reinforcement that require higher response ratios, or across a range of doses. In conclusion, these data indicate that CART is not integral to the effects of psychostimulants in mice lacking CART throughout development, although it may play a regulatory role in the intact animal.