CART (Cocaine and Amphetamine Regulated Transcript) was originally discovered as modulated by cocaine in the striatum. It is of great interest to fully characterize the CARTir cells of the ventral striatum and their projections to further analyze the potential role of CART in the mechanism of action of psychomotor stimulants. CART peptides are a novel family of peptides, which are believed to act as neuropeptide transmitters. Consistent with the distribution of other neuropeptides, immunohistochemical localization studies have identified CART peptides in distinct neuronal populations. One population of CART peptide containing neurons is the medium spiny projection neurons of the shell and core regions of the Acc. These neurons project to several areas in the midbrain, including the VTA and SN. Both the VTA and substantia nigra reticulata (SNr) contain moderate to large densities of CARTir varicosities and terminals. Intra-VTA injection of CART peptide produces physiological effects, which are very likely mediated by DA neurons. We will test the hypothesis that synaptic contact between CARTir terminals and DA neurons in the VTA may be the anatomical basis for these effects. The pattern of distribution of CARTir terminals in the SNr strongly suggests that CART peptides may be part of a specific striatal-nigrothalamic-prefrontal cortical circuit in the brain. The following proposal will provide a complete, detailed description of CART peptide distribution as part of this circuit. Furthermore, CART peptides, like other neuropeptides should be stored in dense core vesicles before they are released from the neuron. To verify this point, analysis of the subcellular localization of CART peptides will be conducted.
