title: 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.
authors.affiliation: Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales, UK. SmithGA@cf.ac.uk
authors.forename: Gaynor A
authors.initials: GA
authors.lastname: Smith
authors.forename: Andreas
authors.initials: A
authors.lastname: Heuer
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Dunnett
authors.forename: Emma L
authors.initials: EL
authors.lastname: Lane
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology; D018491:Dopamine Agonists / Q000494:pharmacology; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D007980:Levodopa / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology*; D045442:Rotarod Performance Test; D013378:Substantia Nigra / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D018663:Adrenergic Agents; D018491:Dopamine Agonists; D007980:Levodopa; D016627:Oxidopamine; D001058:Apomorphine