AUTHOR=Nakamura Takashi , Nishijima Haruo , Mori Fumiaki , Kinoshita Iku , Kon Tomoya , Suzuki Chieko , Wakabayashi Koichi , Tomiyama Masahiko 

TITLE=Axon terminal hypertrophy of striatal projection neurons with levodopa-induced dyskinesia priming

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 17 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1169336

DOI=10.3389/fnins.2023.1169336

ISSN=1662-453X

ABSTRACT=Background: A rat model of levodopa-induced dyskinesia (LID) showed enlarged axon terminals of striatal direct pathway neurons in the internal segment of the globus pallidus (GPi) with excessive gamma-aminobutyric acid (GABA) storage in them. Massive GABA release to GPi upon levodopa administration determines the emergence of LID.
Objectives: We examined whether LID and axon terminal hypertrophy gradually develop with repeated levodopa treatment in Parkinsonian rats to examine if the hypertrophy reflects dyskinesia priming.
Methods: 6-hydroxydopamine-lesioned hemiparkinsonian rats were randomly allocated to receive saline injections (placebo group, 14 days; n = 4), injections of 6 mg/kg levodopa methyl ester combined with 12.5 mg/kg benserazide (levodopa-treated groups, 3-day-treatment; n = 4, 7-day-treatment; n = 4, 14-day-treatment; n = 4), or injections of 6 mg/kg levodopa methyl ester with 12.5 mg/kg benserazide and 1 mg/kg 8-hydroxy-2-(di-n-propylamino)tetralin for 14 days (8-OH-DPAT-treated group; n = 4). We evaluated abnormal involuntary movement (AIM) scores and axon terminals in the GPi.
Results: The AIM score increased with levodopa treatment, as did the hypertrophy of axon terminals in the GPi, showing an increased number of synaptic vesicles in hypertrophied terminals.
Conclusion: Increased GABA storage in axon terminals of the direct pathway neurons represents the priming process of LID.