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

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/Delta FosB was differentially affected in the striatum and nucleus accumbens regions in dyskinetic mice according to lesion type. (C) 2011 Elsevier B.V. All rights reserved.