Basal gangliar dopaminergic neurons contribute importantly to the sensorimotor information processing of humans and animals, with abnormalities at these synapses leading to disorders such as parkinsonism and tardive dyskinesias. The importance of the dopaminergic innervation to the striatum (caudate and putamen) has been widely recognized. Dopamine released in the striatum acts by means of postsynaptic D 2 and D 1 dopamine receptor subtypes, the D 2 effects appearing to be of principle importance. The current proposal is directed toward the understanding of a less well-recognized, but perhaps equally critical, role for dopamine released in the substantia nigra pars reticulata. This zone of the substantia nigra receives the primary efference of the caudate-putamen (through striatonigral fibers), and current evidence suggests that D 1 receptors are associated with the striatonigral axon terminals. Dopamine's action in this region, therefore, could powerfully influence the output of the basal ganglia. The experiments investigate the properties of D1 (and D2 receptors) in the substantia nigra. Light microscopic localization work is proposed to determine the extent to which each receptor subtypes is associated with pars compacta and/or pars reticulata. To gain further evidence concerning localization of these receptor subtypes injection of the microtubule poison colchicine will be made along the axons, and the transport of D, and D, receptors along mesostriatal and striatonigral axons will be investigated. The functional influences of dopamine's action within substantia nigra will be determined by injecting agonists of D1 and D2 receptors into the substantia nigra of one hemisphere of awake animals ana observing effects on motor function (rotation). Also, using [14 C]2-deoxyglucose autoradiography to chart the influences on basal gangliar metabolism, the effects of dopamine D 1 and D 2 agonists in the substantia nigra will be compared.
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