Serotonin 1B receptor stimulation reduces D1 receptor agonist-induced dyskinesia

Dopamine replacement therapy for the treatment of Parkinson's disease leads to deleterious abnormal involuntary movements (AIMs), known as L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia, which parallels enhanced striatal dopamine D1 receptor-mediated signaling. Recent evidence suggest...

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Published inNeuroreport Vol. 20; no. 14; p. 1265
Main Authors Jaunarajs, Karen L Eskow, Dupre, Kristin B, Steiniger, Aimee, Klioueva, Anna, Moore, Alexander, Kelly, Catherine, Bishop, Christopher
Format Journal Article
LanguageEnglish
Published England 23.09.2009
Subjects
Adrenergic Agents
Animals
Benzazepines - toxicity
Dopamine Agonists - toxicity
Dyskinesia, Drug-Induced - drug therapy
Levodopa - adverse effects
Male
Motor Activity - drug effects
Oxidopamine - toxicity
Parkinsonian Disorders - chemically induced
Pyridines - pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Dopamine D1 - agonists
Receptors, Dopamine D1 - metabolism
Serotonin 5-HT1 Receptor Agonists
Serotonin Receptor Agonists - pharmacology
Severity of Illness Index
Time Factors
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Summary:Dopamine replacement therapy for the treatment of Parkinson's disease leads to deleterious abnormal involuntary movements (AIMs), known as L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia, which parallels enhanced striatal dopamine D1 receptor-mediated signaling. Recent evidence suggests stimulation of striatal serotonin (5-HT) 1B receptors may reduce D1-mediated signaling. Given this potential antidyskinetic mechanism, male hemiparkinsonian Sprague-Dawley rats received treatments of D1 receptor agonist, SKF81297, (0.8 mg/kg) or L-DOPA (12 mg/kg, subcutaneous injection). Dyskinetic movements were rated using the AIMs scale. Rats were then administered vehicle (100% dimethyl sulfoxide) or the 5-HT1B receptor agonist, CP94253, (1.5 or 3.0 mg/kg, subcutaneous injection), followed by SKF81297 or L-DOPA and rated for AIMs. Results indicate that CP94253 mitigates both L-DOPA and D1 receptor agonist-induced dyskinesia. These findings suggest that 5-HT1B receptor stimulation directly diminishes D1 receptor-mediated dyskinesia, implicating an important target for the treatment of L-DOPA-induced dyskinesia.
ISSN:1473-558X
DOI:10.1097/WNR.0b013e3283300fd7