Validation of a New Scoring Scale for Behavioral Assessment of L-Dopa-Induced Dyskinesia in the Rat: A New Tool for Early Decision-Making in Drug Development. Loiodice, S., Denibaud, A., Deffains, W., Alix, M., Montagne, P., Seffals, M., & Drieu La Rochelle, C. ACS Chem Neurosci, 9(4):762–772, April, 2018. doi abstract bibtex The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated nonhuman primate (NHP) has been described as the most translatable model for experimental reproduction of L-dopa-induced dyskinesia (LID). However, from a drug discovery perspective, the risk associated with investment in this type of model is high due to the time and cost. The 6-hydroxydopamine (6-OHDA) rat dyskinesia model is recommended for testing compounds but relies on onerous, and nonstandard behavioral rating scales. We sought to develop a simplified and sensitive method aiming at assessing LID in the rat. The purpose was to validate a reliable tool providing earlier insight into the antidyskinetic potential of compounds in a time/cost-effective manner before further investigation in NHP models. Unilaterally 6-OHDA-lesioned rats were administered L-dopa (20 mg/kg) and benserazide (5 mg/kg) daily for 3 weeks starting 4 weeks postlesion, then coadministered with amantadine (20-30-40 mg/kg). An adapted rating scale was used to score LID frequency and a severity coefficient was applied depending on the features of the observed behavior. A gradual increase (about 3-fold) in LID score was observed over the 3 weeks of L-dopa treatment. The rating scale was sensitive enough to highlight a dose-dependent amantadine-mediated decrease (about 2.2-fold) in LID score. We validated a simplified method, able to reflect different levels of severity in the assessment of LID and, thus, provide a reliable tool for drug discovery.
@article{loiodice_validation_2018,
title = {Validation of a {New} {Scoring} {Scale} for {Behavioral} {Assessment} of {L}-{Dopa}-{Induced} {Dyskinesia} in the {Rat}: {A} {New} {Tool} for {Early} {Decision}-{Making} in {Drug} {Development}},
volume = {9},
issn = {1948-7193},
shorttitle = {Validation of a {New} {Scoring} {Scale} for {Behavioral} {Assessment} of {L}-{Dopa}-{Induced} {Dyskinesia} in the {Rat}},
doi = {10.1021/acschemneuro.7b00426},
abstract = {The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated nonhuman primate (NHP) has been described as the most translatable model for experimental reproduction of L-dopa-induced dyskinesia (LID). However, from a drug discovery perspective, the risk associated with investment in this type of model is high due to the time and cost. The 6-hydroxydopamine (6-OHDA) rat dyskinesia model is recommended for testing compounds but relies on onerous, and nonstandard behavioral rating scales. We sought to develop a simplified and sensitive method aiming at assessing LID in the rat. The purpose was to validate a reliable tool providing earlier insight into the antidyskinetic potential of compounds in a time/cost-effective manner before further investigation in NHP models. Unilaterally 6-OHDA-lesioned rats were administered L-dopa (20 mg/kg) and benserazide (5 mg/kg) daily for 3 weeks starting 4 weeks postlesion, then coadministered with amantadine (20-30-40 mg/kg). An adapted rating scale was used to score LID frequency and a severity coefficient was applied depending on the features of the observed behavior. A gradual increase (about 3-fold) in LID score was observed over the 3 weeks of L-dopa treatment. The rating scale was sensitive enough to highlight a dose-dependent amantadine-mediated decrease (about 2.2-fold) in LID score. We validated a simplified method, able to reflect different levels of severity in the assessment of LID and, thus, provide a reliable tool for drug discovery.},
language = {eng},
number = {4},
journal = {ACS Chem Neurosci},
author = {Loiodice, Simon and Denibaud, Anne-Sophie and Deffains, Wendy and Alix, Magali and Montagne, Pierre and Seffals, Marine and Drieu La Rochelle, Christophe},
month = apr,
year = {2018},
pmid = {29226687},
keywords = {6-OHDA, Amantadine, Animals, Antiparkinson Agents, Behavior Rating Scale, Behavior, Animal, Disease Models, Animal, Drug Development, drug discovery, dyskinesia, Dyskinesia, Drug-Induced, L-dopa, Parkinson Disease, Parkinson’s disease, Rats},
pages = {762--772},
file = {Version soumise:D\:\\Home\\maguillout\\Zotero\\Donnees\\storage\\P9E6MYP7\\Loiodice et al. - 2018 - Validation of a New Scoring Scale for Behavioral A.pdf:application/pdf},
}
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However, from a drug discovery perspective, the risk associated with investment in this type of model is high due to the time and cost. The 6-hydroxydopamine (6-OHDA) rat dyskinesia model is recommended for testing compounds but relies on onerous, and nonstandard behavioral rating scales. We sought to develop a simplified and sensitive method aiming at assessing LID in the rat. The purpose was to validate a reliable tool providing earlier insight into the antidyskinetic potential of compounds in a time/cost-effective manner before further investigation in NHP models. Unilaterally 6-OHDA-lesioned rats were administered L-dopa (20 mg/kg) and benserazide (5 mg/kg) daily for 3 weeks starting 4 weeks postlesion, then coadministered with amantadine (20-30-40 mg/kg). An adapted rating scale was used to score LID frequency and a severity coefficient was applied depending on the features of the observed behavior. 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