CART and the Dopamine System in the Nucleus Accumbens

Emory University, Atlanta GA

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Abstract

DESCRIPTION (provided by applicant): CART (cocaine- amphetamine-regulated transcript) was discovered as an mRNA up-regulated in ventral striatum after acute cocaine and amphetamine. Further studies have shown the peptide and mRNA are expressed at high levels in the projection neurons of the nucleus accumbens (NA), particularly in the shell. Furthermore these neurons appear to receive input from dopamine terminals originating in the VTA. Increases in locomotion result from intra-VTA injection of CART peptide, an effect which is blocked by haloperidol. These data suggest a relationship between CART neurons in the NA and the mesolimbic dopamine system. No CART receptor is yet known. The aim of this study is to test the hypothesis that CART and the dopamine (DA) system interact in the NA. Using double in situ hybridization, it will be determined if CART co-localizes with dopamine receptors in cells of the NA. To examine if DA regulates CART, CART mRNA and peptide will be measured. The interaction will be tested using 6-OHDA lesions, and local and systemic injection of dopamine receptor selective agonists and antagonists.