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.
Texto completo:
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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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