Exercise decreases aberrant corticostriatal plasticity in an animal model of L-DOPA-induced dyskinesia

Abstract

Physical exercise attenuates the development of L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) in 6-hydroxy-dopamine-induced hemiparkinsonian mice through unknown mechanisms. We now tested if exercise normalizes the aberrant corticostriatal neuroplasticity associated with experimental murine models of LID. C57BL/6 mice received two unilateral intrastriatal injections of 6-hydroxydopamine (12 μg) and were treated after 3 wk with L-DOPA/benserazide (25/12.5 mg/kg) for 4 wk, with individualized moderate-intensity running (60%-70% V_ O2peak) or not (untrained). L-DOPA converted the pattern of plasticity in corticostriatal synapses from a long-term depression (LTD) into a long-term potentiation (LTP). Exercise reduced LID severity and decreased aberrant LTP. These results suggest that exercise attenuates abnormal corticostriatal plasticity to decrease LID.