Archival ReportAntagonizing L-type Ca2+ Channel Reduces Development of Abnormal Involuntary Movement in the Rat Model of L-3,4-Dihydroxyphenylalanine-Induced Dyskinesia
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Animals
Male Wistar rats (Harlan Winkelmann, Borchen, Germany) weighing 280–320 g were housed in groups of five in Macrolon type III cages under standard laboratory conditions (22 ± 1 C°, 55 ± 5% of a relative humidity, and a 12-hour light–dark cycle) with ad libitum access to food (GLP Vitamin fortified; Provimi Kliba AG, Kaiseraugst, Switzerland) and water. All experiments were approved by the Ethical Committee of the regional council of Upper Swabia (Tübingen, Germany) and by the Malmö-Lund ethical
Isradipine Treatment Reduces L-DOPA-Induced AIMs
A pilot experiment (Exp I in Figure 1) was performed at a therapeutically relevant dose of isradipine (.1 mg/kg/day). When animals were OFF L-DOPA, no difference was observed among the 6-OHDA-only, the 6-OHDA-placebo pellet, and the 6-OHDA-Isradipine pellet groups, suggesting isradipine exposure had no noticeable side effects. During the AIM rating sessions, the 6-OHDA-isradipine group developed less severe turning behavior than the two control groups, namely the 6-OHDA-only and the
Discussion
The present study shows that treatment with isradipine dose-dependently attenuates L-DOPA-induced rotational locomotion and AIM scores, provided that the exposure to isradipine starts soon after a 6-OHDA lesion of the nigrostriatal fiber bundle. Dendritic spine counting at the EM level showed that this treatment (isradipine, .2 mg/kg/day) prevented the 6-OHDA-induced spine loss in D1-negative MSNs and normalized PPE-A mRNA expression. In contrast, isradipine had no effect on L-DOPA-induced
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