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 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.
Taylor
Jennifer L
JL
Cellular and Clinical Neurobiology Program, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Bishop
Christopher
C
Walker
Paul D
PD
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000172:deficiency / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007980:Levodopa / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D012457:Salicylamides / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism
D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; D016627:Oxidopamine; C045989:eticlopride; D004298:Dopamine; D009638:Norepinephrine