Role of dopamine D4 receptors in motor hyperactivity induced by neonatal 6-hydroxydopamine lesions in rats

Abstract

The role of dopamine D4 receptors in behavioral hyperactivity was investigated by assessing D4 receptor expression in brain regions and behavioral effects of D4 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 D4 but not D2 receptor levels in caudate-putamen. D4-selective antagonist CP-293,019 dose-dependently reversed lesion-induced hyperactivity, and D4-agonist CP-226,269 increased it. These results indicate a physiological role of dopamine D4 receptors in motor behavior, and may suggest much-needed innovative treatments for ADHD. © 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.