Imaging SERT Availability in a Rat Model of L-DOPA-Induced Dyskinesia.

Abstract

The development of L-DOPA-induced dyskinesia (LID) is one of the most severe side effects of chronic L-DOPA treatment in Parkinson's disease patients. [11C]DASB positron emission tomography (PET) provides a prominent tool to visualize and quantify serotonin transporter (SERT) pathology in vivo in patients and in animal models. To evaluate the effect of chronic L-DOPA treatment on SERT availability in an animal model of LID, we performed a longitudinal PET study. Rats received a unilateral 6-hydroxydopamine (6-OHDA) lesion, and striatal and extrastriatal SERT expression levels were studied with [11C]DASB, a marker of SERT availability, before and after daily treatment with L-DOPA. Dyskinesias were evaluated at different time points over a period of 21days. [11C]DASB binding was found to be decreased after 6-OHDA lesions in the striatum, cortex, and hippocampus 5weeks after 6-OHDA injection in the lesioned hemisphere of the rat brain. Chronic L-DOPA priming resulted in a relative preservation of SERT availability in the lesioned and healthy hemisphere compared to baseline measurements. Our longitudinal PET data support a preservation of SERT availability after the induction of L-DOPA-induced dyskinesia, which is in line with previous reports in dyskinetic PD patients.