Role of dopamine D(4) receptors in motor hyperactivity induced by neonatal 6-hydroxydopamine lesions in rats

  • Zhang K
  • Tarazi F
  • Baldessarini R
  • 37

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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.

Author-supplied keywords

  • *Membrane Glycoproteins
  • *Nerve Tissue Proteins
  • Animals
  • Animals, Newborn/*physiology
  • Autoradiography
  • Central Nervous System Stimulants/pharmacology
  • Dopamine Agonists
  • Dopamine Antagonists/pharmacology
  • Dopamine Plasma Membrane Transport Proteins
  • Hyperkinesis/*chemically induced
  • Ligands
  • Membrane Transport Proteins/metabolism
  • Motor Activity/drug effects
  • Oxidopamine/*pharmacology
  • Pyrazines/pharmacology
  • Pyrimidines/pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1/drug effects/physiology
  • Receptors, Dopamine D2/agonists/antagonists & inhi
  • Receptors, Dopamine D4
  • Sympatholytics/*pharmacology

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Authors

  • K Zhang

  • F I Tarazi

  • R J Baldessarini

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