Role of dopamine D(4) receptors in motor hyperactivity induced by neonatal 6-hydroxydopamine lesions in rats.
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.
Zhang
K
K
Mailman Research Center, McLean Division of Massachusetts General Hospital, 115 Mill Street, Belmont, MA 02478, USA. kz@mclean.harvard.edu
Tarazi
F I
FI
Baldessarini
R J
RJ
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001345:Autoradiography; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D018491:Dopamine Agonists; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D006948:Hyperkinesis / Q000139:chemically induced*; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins; D016627:Oxidopamine / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*; D050638:Receptors, Dopamine D4; D013565:Sympatholytics / Q000494:pharmacology*
C111732:CP 293019; D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; C493601:Drd4 protein, rat; D008024:Ligands; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011719:Pyrazines; D011743:Pyrimidines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013565:Sympatholytics; D050638:Receptors, Dopamine D4; D016627:Oxidopamine