Abstract
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.
MeSH terms
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Animals
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Animals, Newborn / physiology*
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Autoradiography
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Central Nervous System Stimulants / pharmacology
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Dopamine Agonists
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Dopamine Antagonists / pharmacology
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Dopamine D2 Receptor Antagonists
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Dopamine Plasma Membrane Transport Proteins
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Hyperkinesis / chemically induced*
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Ligands
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Membrane Glycoproteins*
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Membrane Transport Proteins / metabolism
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Motor Activity / drug effects
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Nerve Tissue Proteins*
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Oxidopamine / pharmacology*
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Pyrazines / pharmacology
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Pyrimidines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Dopamine D1 / drug effects
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Receptors, Dopamine D1 / physiology
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Receptors, Dopamine D2 / agonists
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Receptors, Dopamine D2 / physiology*
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Receptors, Dopamine D4
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Sympatholytics / pharmacology*
Substances
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CP 293019
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Central Nervous System Stimulants
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Dopamine Agonists
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Dopamine Antagonists
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Dopamine D2 Receptor Antagonists
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Dopamine Plasma Membrane Transport Proteins
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Drd4 protein, rat
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Ligands
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Membrane Glycoproteins
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Pyrazines
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Pyrimidines
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Receptors, Dopamine D1
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Receptors, Dopamine D2
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Sympatholytics
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Receptors, Dopamine D4
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Oxidopamine