The role of dopamine D(4) receptors in behavioral hyperactivity was investigated by assessing D(4) receptor expression in brain regions and behavioral effects of D(4) receptor-selective ligands in juvenile rats with neonatal 6-hydroxydopamine lesions, a laboratory model for attention deficit-hyperactivity disorder (ADHD). Autoradiographic analysis indicated that motor hyperactivity in lesioned rats was closely correlated with increases in D(4) but not D(2) receptor levels in caudate-putamen. D(4)-selective antagonist CP-293,019 dose-dependently reversed lesion-induced hyperactivity, and D(4)-agonist CP-226,269 increased it. These results indicate a physiological role of dopamine D(4) receptors in motor behavior, and may suggest much-needed innovative treatments for ADHD.
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