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Unilateral nigrostriatal 6-hydroxydopamine lesions in mice II: Predicting L-DOPA-induced dyskinesia

Smith, Gaynor A., Heuer, Andreas, Dunnett, Stephen Bruce and Lane, Emma Louise 2012. Unilateral nigrostriatal 6-hydroxydopamine lesions in mice II: Predicting L-DOPA-induced dyskinesia. Behavioural Brain Research 226 (1) , pp. 281-292. 10.1016/j.bbr.2011.09.025

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In the 6-hydroxydopamine (6-OHDA) lesioned rodent the location of the lesion produces significantly different behavioural phenotypes, responses to the dopamine precursor l-3,4-dihydroxyphenylalanine (l-DOPA) and neuropathology. Lesion extent is commonly determined by a series of motor tests, but whether any of these tests have a relationship to the development and predictability of dyskinesia is unknown. We used mice with 6-OHDA lesions of the striatum, medial forebrain bundle and substantia nigra to examine the relationship between a range of tests used to determine motor function in the absence of l-DOPA: rotarod, cylinder, corridor, the balance beam, locomotor activity, psycho-stimulant and spontaneous rotational behaviour. The mice were subsequently treated with l-DOPA in progressively increasing doses and the development of l-DOPA-induced dyskinesia assessed. Most of these tests predict dopamine depletion but only rotarod, spontaneous rotations, apomorphine-induced rotations and locomotor activities were significantly correlated with the development of dyskinesia at 6 mg/kg and 25 mg/kg l-DOPA. The losses of dopaminergic neurons and serotonergic density in the ventral and dorsal striatum were dependent upon lesion type and were also correlated with l-DOPA-induced dyskinesia. The expression of FosB/ΔFosB was differentially affected in the striatum and nucleus accumbens regions in dyskinetic mice according to lesion type.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: Q Science > QH Natural history > QH301 Biology
R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords: l-3,4-dihydroxyphenylalanine; Dyskinesia; 6-Hydroxydopamine; TH; 5-HT; FosB
Publisher: Elsevier
ISSN: 0166-4328
Last Modified: 04 Feb 2020 23:20

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