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

Abstract

Using a rat model of L-DOPA-induced dyskinesia (LID), the contributions of dopamine D1 and D2 receptors to axial, limb, and orolingual (ALO) abnormal involuntary movements (AIMs) elicited by L-DOPA were examined. Chronic L-DOPA-treated rats received the D1 receptor antagonist SCH23390 (0.01, 0.1, and 1.0 mg/kg; i.p.), the D2 receptor antagonist Eticlopride (0.01, 0.1, and 1.0 mg/kg; i.p.), a mixture of both antagonists (0.01, 0.1, 1.0 mg/kg each; i.p.), or vehicle 30 min prior to L-DOPA (6 mg/kg; i.p.)+Benserazide (15 mg/kg; i.p.). SCH23390 (0.1 and 1.0 mg/kg) significantly reduced axial and limb AIMs, while the same doses of Eticlopride 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 mg/kg) AIMs. These results indicate the importance of D1 and D2 receptors to LID and further validate the rat AIMs model.

• Authors: Jennifer L Taylor, Christopher Bishop, Paul D Walker
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 81 Issue 4 Pg. 887-93 (Aug 2005) ISSN: 0091-3057 [Print] United States
• PMID: 16023708 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benzazepines
• Dopamine Antagonists
• Dopamine D2 Receptor Antagonists
• Receptors, Dopamine D1
• Receptors, Dopamine D2
• Salicylamides
• 3,4-Dihydroxyphenylacetic Acid
• Serotonin
• Levodopa
• Hydroxyindoleacetic Acid
• Oxidopamine
• eticlopride
• Dopamine
• Norepinephrine

Topics

• 3,4-Dihydroxyphenylacetic Acid (metabolism)
• Analysis of Variance
• Animals
• Behavior, Animal (drug effects)
• Benzazepines (pharmacology)
• Corpus Striatum (drug effects, metabolism)
• Dopamine (deficiency, metabolism)
• Dopamine Antagonists (pharmacology)
• Dopamine D2 Receptor Antagonists
• Dose-Response Relationship, Drug
• Drug Synergism
• Dyskinesia, Drug-Induced (etiology, physiopathology, prevention & control)
• Hydroxyindoleacetic Acid (metabolism)
• Levodopa (adverse effects, therapeutic use)
• Male
• Norepinephrine (metabolism)
• Oxidopamine (toxicity)
• Parkinson Disease, Secondary (chemically induced, drug therapy)
• Rats
• Rats, Sprague-Dawley
• Receptors, Dopamine D1 (antagonists & inhibitors, physiology)
• Receptors, Dopamine D2 (physiology)
• Salicylamides (pharmacology)
• Serotonin (metabolism)