Damage to the dopaminergic innervation of the rat neostriatum results in impaired sensorimotor performance, including an inability to orient toward somatosensory stimuli. Many rats with such damage show a recovery from their initial sensorimotor impairments, and this recovery appears to be accomplished by a normalization of transmission at neostriatal dopamine terminals that escape injury. This recovery is mediated by presynaptic and postsynaptic changes at these surviving synapses. This proposal seeks to understand the cellular basis of this recovery by three experimental lines. (1) An important advance would be to determine which region of the neostriatum subserves orientation to touch, thereby restricting the neostriatal zones in which cellular correlates of the recovery would be sought. Experiments are proposed that use cats and rats to find the neostriatal locus of the somatonsensory orientation. (2) Postsynaptic changes that contribute to this recovery result from a proliferation of neostriatal dopamine receptors. Some of these receptors are labelled by incubation with 3H-spiroperidol. An autoradiographic approach to determine the binding of 3H-spiroperidol to forebrain sections through the neostriatum is described, as is the video imaging and analysis system used in the quantification of this binding. These methods will be used to determine the time course and topography of the proliferation of 3H-spiroperidol binding sites in the neostriatum of rats recovering sensorimotor functions after damage to the dopaminergic afferents. (3) The contribution that a loss of dopamine uptake sites may play to the early recovery of somatosensory function is determined using pharmacological approaches. The results will provide new evidence concerning the topographic organization of the caudate-putamen, which will guide research on the neuropathology and chemopathology of basal ganglia movement disorders. The 3H-spiroperidol autoradiography method to demonstrate dopamine receptor supersensitivity has important potential clinical applications.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Neurology B Subcommittee 1 (NEUB)
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University of California Irvine
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LaHoste, G J; Marshall, J F (1991) Chronic eticlopride and dopamine denervation induce equal nonadditive increases in striatal D2 receptor density: autoradiographic evidence against the dual mechanism hypothesis. Neuroscience 41:473-81
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LaHoste, G J; Marshall, J F (1989) Non-additivity of D2 receptor proliferation induced by dopamine denervation and chronic selective antagonist administration: evidence from quantitative autoradiography indicates a single mechanism of action. Brain Res 502:223-32
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