Cocaine-and-amphetamine-regulated-transcript (CART) was originally discovered in the nucleus accumbens (NA) following acute psychostimulant administration. Further localization studies of CART mRNA and peptide revealed CART in other reward/reinforcement nuclei such as the ventral tegrnental area (VTA), the ventral pallidum (VP), and the lateral hypothalamus (LH). Subsequent behavioral studies support the role of CART in drug addiction and hypothalamically-mediated feeding behavior. Since the CART peptide plays a pivotal role in motivational behaviors and the mesolimbic dopaminergic reward pathway, we decided that additional neuroanatomical studies were crucial at this time to further delineate the circuitry, ultrastructural features and synaptology of CART-containing elements. We will test the hypothesis that CART-containing neurons in the LH have a significant neuroanatomical relationship (indirect or direct) with the mesolimbic dopaminergic system and other nuclei involved in mediating the rewarding/reinforcing effects of drugs of abuse and natural rewards such as food. Tracing studies combined with immunocytochemistry will be utilized to determine two factors: the abundance of CART-containing projections from the LH to the VTA and the extrinsic projections synapsing upon the LH CART neurons. In situ hybridization will provide a functional approach to discovering the effect of NA shell and/or VP neurons on LH CART mRNA expression in the LH.
