Dopamine D1 and D2 receptor contributions to L-DOPA-induced dyskinesia in the dopamine-depleted rat

Using a rat model of L-DOPA-induced dyskinesia (LID), the contributions of dopamine D-1 and D-2 receptors to axial, limb, and orolingual (ALO) abnormal involuntary movements (AIMs) elicited by L-DOPA were examined. Chronic L-DOPA-treated rats received the D, receptor antagonist SCH23390 (0,01, 0.1, and 1.0 mg/kg; ip), the D-2 receptor antagonist Eficlopride (0.01, 0.1, and 1.0 mgikg; ip), a mixture of both antagonists (0.01, 0.1, 1.0 mg/kg each; ip), or vehicle 30 min prior to L-DOPA (6 mg/kg; ip)+Benserazide (15 mg/kg; ip). SCH23390 (0.1 and 1.0 mg/kg) significantly reduced axial and limb AlMs, while the same doses of Eficlopride significantly decreased axial, limb, and orolingual AIMs. Co-administration of SCH23390+Eticlopride significantly reduced axial (0.01, 0.1 and 1.0 mg/kg), limb (0.1 and 1.0 mg/ kg), and orolingual (0.1 and 1.0 mgikg) AlMs. These results indicate the importance of D, and D2 receptors to LID and further validate the rat AIMs model. (c) 2005 Elsevier Inc. All rights reserved.