Generation of a model of l-DOPA-induced dyskinesia in two different mouse strains

Prolonged use of the dopamine precursor l-DOPA for the treatment of Parkinson's disease commonly results in abnormal involuntary movements, which are termed l-DOPA-induced dyskinesia (LID). Over-activity at corticostriatal synapses onto neurons of the direct and indirect striatal output pathways has been implicated in the development of dyskinesia, but it has proved difficult to investigate the pathways separately due to their morphological similarities. The recent development of bacterial artificial chromosome mice that express green fluorescent protein in either the direct or indirect pathway allows visual identification of the output neurons in each pathway.Here we describe the use of two different strains of these transgenic mice (pure FVB and FVB crossed with C57B1/6) in the development of mouse models of l-DOPA-induced dyskinesia. This model will allow the direct and indirect pathways to be studied individually to delineate the cellular and molecular mechanisms underlying dyskinesias. These studies demonstrate that mouse strain impacts on behavioural responses and l-DOPA sensitivity. Therefore, when generating mouse models of LID, strain must be taken into consideration when choosing the l-DOPA dosing regimen.

► Both FVB and FVB/C57B1/6 BAC mice can be used for unilaterally lesioned 6-OHDA mouse models of PD. ► In 6-OHDA mice of both strains, l-DOPA (4.5 mg/kg b.i.d.) for 21 days induces AIMs. ► The EC50 of l-DOPA is lower in FVB/C57B1/6 mice compared with pure FVB mice. ► Mouse strain must be taken into account when generating mouse models of LID. ► These models will be useful for studying mechanisms of LID in BAC transgenic mice.