L-DOPA-elicited abnormal involuntary movements in the rats damaged severely in substantia nigra by 6-hydroxydopamine.
6-hydroxydopamine (6-OHDA)
Parkinson’s disease (PD)
abnormal involuntary movements (AIMs)
dyskinesia
levodopa (L-DOPA)
Journal
Annals of palliative medicine
ISSN: 2224-5839
Titre abrégé: Ann Palliat Med
Pays: China
ID NLM: 101585484
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
received:
12
02
2020
accepted:
09
03
2020
pubmed:
14
4
2020
medline:
25
2
2021
entrez:
14
4
2020
Statut:
ppublish
Résumé
Dyskinesia of rat models can occur in several conditions: acute levodopa (L-DOPA) administration provided that the drug dose is sufficiently high and/or that the nigrostriatal dopamine (DA) pathway is seriously damaged, and repeated L-DOPA administration which could cause a reduction of the dyskinesia-threshold dose, a progressive aggravation and an increasing incidence of dyskinesia. Therefore, if the damage of the nigrostriatal DA pathway is extremely severe, what abnormal movements can be elicited by first injecting L-DOPA or other dopaminergic agonists? The problem deserves exploring. Rat models with damage of varying severity were divided into three groups: the serious lesion [induced by 40 µg 6-hydroxydopamine (6-OHDA), two injected coordinates including substantia nigra (SN) and medial forebrain bundle], the moderate lesion (20 µg 6-OHDA, a coordinate in SN) and the control. Three weeks after lesion, the Rota Rad test and Cylinder test were performed to assess the motor activities of rat models, the abnormal involuntary movements (AIMs) elicited by L-DOPA or apomorphine (APO) were observed, and the dopaminergic degeneration in SN and striatum was determined. Both seriously lesioned rats and the moderately were observed to exhibit a significant decrease in motor activities. In the rats with a serious lesion, scarcely any dopaminergic neurons were present in the SN, tissue DA level decreased by 99% in the striatum, and both L-DOPA and APO could elicit AIMs and rotational movements. In the rats with the moderate lesion, only rotation movements could be elicited. The rotation speed of moderately lesioned rats was 9 turns/min, but that of seriously was only 4.5 turns/min elicited by APO. Both dyskinesia and rotation movement are the specific expressions elicited by L-DOPA or APO in rats whose SN is damaged by 6-OHDA. Dyskinesia reflects more severe damage than rotation movement.
Sections du résumé
BACKGROUND
BACKGROUND
Dyskinesia of rat models can occur in several conditions: acute levodopa (L-DOPA) administration provided that the drug dose is sufficiently high and/or that the nigrostriatal dopamine (DA) pathway is seriously damaged, and repeated L-DOPA administration which could cause a reduction of the dyskinesia-threshold dose, a progressive aggravation and an increasing incidence of dyskinesia. Therefore, if the damage of the nigrostriatal DA pathway is extremely severe, what abnormal movements can be elicited by first injecting L-DOPA or other dopaminergic agonists? The problem deserves exploring.
METHODS
METHODS
Rat models with damage of varying severity were divided into three groups: the serious lesion [induced by 40 µg 6-hydroxydopamine (6-OHDA), two injected coordinates including substantia nigra (SN) and medial forebrain bundle], the moderate lesion (20 µg 6-OHDA, a coordinate in SN) and the control. Three weeks after lesion, the Rota Rad test and Cylinder test were performed to assess the motor activities of rat models, the abnormal involuntary movements (AIMs) elicited by L-DOPA or apomorphine (APO) were observed, and the dopaminergic degeneration in SN and striatum was determined.
RESULTS
RESULTS
Both seriously lesioned rats and the moderately were observed to exhibit a significant decrease in motor activities. In the rats with a serious lesion, scarcely any dopaminergic neurons were present in the SN, tissue DA level decreased by 99% in the striatum, and both L-DOPA and APO could elicit AIMs and rotational movements. In the rats with the moderate lesion, only rotation movements could be elicited. The rotation speed of moderately lesioned rats was 9 turns/min, but that of seriously was only 4.5 turns/min elicited by APO.
CONCLUSIONS
CONCLUSIONS
Both dyskinesia and rotation movement are the specific expressions elicited by L-DOPA or APO in rats whose SN is damaged by 6-OHDA. Dyskinesia reflects more severe damage than rotation movement.
Identifiants
pubmed: 32279520
pii: apm.2020.03.32
doi: 10.21037/apm.2020.03.32
doi:
Substances chimiques
Levodopa
46627O600J
Oxidopamine
8HW4YBZ748
Apomorphine
N21FAR7B4S
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM