title: The course of dyskinesia induction by different treatment schedules of levodopa in Parkinsonian rats: is continuous dopaminergic stimulation necessary?
abstract: The aim of the present study was to investigate the course of levodopa induced dyskinesia (LID) development in parkinsonian rats treated with several different levodopa dosing regiments. Administration of 6.25 mg/kg levodopa once daily did not induce any dyskinesia for the first 12.5 +/- 2.5 days. Then, LID gradually increased in intensity reaching an AIMs score on day 40 of 6.3 +/- 0.9. Treatment with 6.25 mg/kg of levodopa qid resulted in the rapid appearance of LID with a mean latency of 2 days and an AIMs score of 19.9 +/- 2.9 on day 10. Levodopa (25 mg/kg) once daily induced severe LID from the second day of treatment reaching an AIMs score of 35 +/- 3.2. In summary, the worst way for delivering levodopa was through intermittent administration of high doses. The daily cumulative dose of levodopa was found more important for LID induction than the total amount of levodopa received. In contrast, the best way to administer levodopa in respect to prevention/delay of LID was "low dopaminergic stimulation" with one low daily dose, instead of trying to achieve "continuous dopaminergic stimulation" using several levodopa doses throughout the day. The benefits of this strategy offered protection against severe dyskinesia even if subsequently subjects were switched to high dose levodopa.
authors.affiliation: Department of Neurology, Medical School, University Of Ioannina, Ioannina, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Tsironis
authors.affiliation: Department of Pharmacology, Medical School, University Of Ioannina, Ioannina, Greece.
authors.forename: Marios
authors.initials: M
authors.lastname: Marselos
authors.affiliation: Department of Physiology, Medical School, University Of Ioannina, Ioannina, Greece.
authors.forename: Angelos
authors.initials: A
authors.lastname: Evangelou
authors.affiliation: Department of Neurology, Medical School, University Of Ioannina, Ioannina, Greece.
authors.forename: Spiridon
authors.initials: S
authors.lastname: Konitsiotis
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000473:pathology; D018491:Dopamine Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004409:Dyskinesia, Drug-Induced / Q000209:etiology*; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018491:Dopamine Agonists; D007980:Levodopa