The mechanisms by which nigrostriatal dopamine (DA) transmission engages the corpus striatal circuitry and ultimately affects its output have been of cardinal interest for several years because of the role of DA in extrapyramidal movement disorders and certain derailments of cognitive function in humans. In the past decade, receptor-binding studies, immunohistochemical studies on the distributions of some neuroactive peptides and transmitter-related enzymes, and anatomical studies of striatal inputs have suggested a high degree of compartmentation in the striatum. Moreover, striatal outputs have been distinguished on anatomical and neurochemical grounds and display at least at least a dual organization that is correlated with the different functional roles of the corpus striatal output structures. The actions of DA within the striatum can be mediated by at least two classes of DA receptor termed D1 and D2. The problem of how DA transmission, mediated by these tow classes of DA receptor, influences chemically and connectionally distinct neurons in the various striatal compartments, and how these compartmentalized cell populations relate to one another, and to distinct striatal inputs and outputs is the focus of the proposed anatomical-pharmacological research projects. We will use a quantitative, radioimmunocytochemical technique as well as standard immunocytochemical, radioligand- binding, in situ hybridization and experimental neuroanatomical techniques, alone and in combination, and drug manipulations with selective D1 and D2 agonists and antagonists to assess these relationships in the mammalian brain. The studies will be done in adult cats and rats. These studies will shed light on the manner in which DA released from nigrostriatal terminals interacts with DA receptors and, consequently, neurochemically distinct striatal output pathways. More generally, the increased understanding of functional mechanisms within the corpus striatum will contribute to the scientific basis for the study of clinical disorders associated with corpus striatal dysfunctions.
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