Unilateral nigrostriatal 6-hydroxydopamine lesions in mice II: predicting l-DOPA-induced dyskinesia.

Abstract:

: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 6mg/kg and 25mg/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.

journal_name

Behav Brain Res

authors

Smith GA,Heuer A,Dunnett SB,Lane EL

doi

10.1016/j.bbr.2011.09.025

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

281-92

issue

1

eissn

0166-4328

issn

1872-7549

pii

S0166-4328(11)00695-4

journal_volume

226

pub_type

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