Repetitive Levodopa Treatment Drives Cell Type-Specific Striatal Adaptations Associated With Progressive Dyskinesia in Parkinsonian Mice

Repeated levodopa treatment in the 6-OHDA mouse model links LID worsening to potentiation of levodopa-evoked responses in both D1- and D2-expressing medium spiny neurons.

• Why it matters: Levodopa-induced dyskinesia and motor fluctuations worsen with disease progression and repeated dosing, but the circuit mechanisms behind this progression are unclear.
• What they did: Using in vivo and ex vivo recordings in 6-OHDA mice, the study isolated effects of repeated treatment on LID worsening and motor responses, testing dopamine release and MSN intrinsic excitability.
• The result: LID worsening is associated with strengthened glutamatergic synapses onto D1-MSNs, and D2-MSN activity changes are linked to LID duration and reduced D2R sensitivity.