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 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.
Jaunarajs
Karen L Eskow
KL
Department of Psychology, Binghamton University, State University of New York, Binghamton, New York 13902, USA.
Dupre
Kristin B
KB
Steiniger
Aimee
A
Klioueva
Anna
A
Moore
Alexander
A
Kelly
Catherine
C
Bishop
Christopher
C
D018663:Adrenergic Agents; D000818:Animals; D001552:Benzazepines / Q000633:toxicity; D018491:Dopamine Agonists / Q000633:toxicity; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D007980:Levodopa / Q000009:adverse effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012720:Severity of Illness Index; D013997:Time Factors
D018663:Adrenergic Agents; D001552:Benzazepines; C097067:CP 94253; D018491:Dopamine Agonists; D011725:Pyridines; D017447:Receptors, Dopamine D1; D058825:Serotonin 5-HT1 Receptor Agonists; D017366:Serotonin Receptor Agonists; D007980:Levodopa; C067113:SK&F 81297; D016627:Oxidopamine