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The Dynamics of Dopamine D2 Receptor-Expressing Striatal Neurons and the Downstream Circuit Underlying L-Dopa-Induced Dyskinesia in Rats / 神经科学通报·英文版
Neuroscience Bulletin ; (6): 1411-1425, 2023.
Artigo em Inglês | WPRIM | ID: wpr-1010621
ABSTRACT
L-dopa (l-3,4-dihydroxyphenylalanine)-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy for Parkinson's disease. The potential contribution of striatal D2 receptor (D2R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear. In this study, we investigated the role of striatal D2R+ neurons and downstream globus pallidus externa (GPe) neurons in a rat model of LID. Intrastriatal administration of raclopride, a D2R antagonist, significantly inhibited dyskinetic behavior, while intrastriatal administration of pramipexole, a D2-like receptor agonist, yielded aggravation of dyskinesia in LID rats. Fiber photometry revealed the overinhibition of striatal D2R+ neurons and hyperactivity of downstream GPe neurons during the dyskinetic phase of LID rats. In contrast, the striatal D2R+ neurons showed intermittent synchronized overactivity in the decay phase of dyskinesia. Consistent with the above findings, optogenetic activation of striatal D2R+ neurons or their projections in the GPe was adequate to suppress most of the dyskinetic behaviors of LID rats. Our data demonstrate that the aberrant activity of striatal D2R+ neurons and downstream GPe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats.
Assuntos

Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Dopamina / Levodopa / Oxidopamina / Receptores de Dopamina D2 / Corpo Estriado / Transtornos Parkinsonianos / Discinesia Induzida por Medicamentos / Neurônios / Antiparkinsonianos Limite: Animais Idioma: Inglês Revista: Neuroscience Bulletin Ano de publicação: 2023 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Dopamina / Levodopa / Oxidopamina / Receptores de Dopamina D2 / Corpo Estriado / Transtornos Parkinsonianos / Discinesia Induzida por Medicamentos / Neurônios / Antiparkinsonianos Limite: Animais Idioma: Inglês Revista: Neuroscience Bulletin Ano de publicação: 2023 Tipo de documento: Artigo