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

Am J Physiol Regul Integr Comp Physiol. 2021 Apr 1;320(4):R541-R546. doi: 10.1152/ajpregu.00295.2020. Epub 2021 Feb 3.

Abstract

Physical exercise attenuates the development of l-3,4-dihydroxyphenylalanine (l-DOPA)-induced dyskinesia (LID) in 6-hydroxydopamine-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% V̇o2peak) 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.

Keywords: corticostriatal plasticity; dyskinesia; l-DOPA-induced dyskinesia; physical exercise.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparkinson Agents / toxicity*
  • Benserazide / toxicity
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / physiopathology
  • Corpus Striatum / drug effects*
  • Corpus Striatum / physiopathology
  • Dihydroxyphenylalanine / analogs & derivatives
  • Disease Models, Animal
  • Dyskinesia, Drug-Induced / etiology
  • Dyskinesia, Drug-Induced / physiopathology
  • Dyskinesia, Drug-Induced / prevention & control*
  • Exercise Therapy*
  • Levodopa / toxicity*
  • Long-Term Potentiation / drug effects
  • Long-Term Synaptic Depression / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Neuronal Plasticity / drug effects*
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / physiopathology
  • Running
  • Time Factors

Substances

  • Antiparkinson Agents
  • 6-hydroxydopa
  • Levodopa
  • Dihydroxyphenylalanine
  • Benserazide