title: Nigral 6-hydroxydopamine lesion impairs performance in a lateralised choice reaction time task--impact of training and task parameters.
abstract: Unilateral intrastriatal and intra-medial forebrain bundle injections of 6-OHDA impair the performance in a lateralised choice reaction time task. However, the extent and pattern of deficits after nigral 6-OHDA injections is less well studied, as well as the impact of training regime or the modification of various task parameters. The nigral 6-OHDA lesion resulted in impaired response accuracy and an increased time to react to and execute the response on the side contralateral to the lesion as compared to sham-lesioned controls. Pre-training of the rats on the task prior to the lesion resulted in slightly faster reaction times as well as a reduced number of preservative panel presses compared to when rats were trained after the 6-OHDA injection. When the rat had to perform a longer sustained nose poke before responding to the lateralised stimuli, the number of useable trials was reduced in both controls and 6-OHDA rats as a result of an increased number of premature withdrawals from the centre hole. This study demonstrates that rats with a nigral 6-OHDA lesion display several distinct deficits in this operant task, which are similar to those seen after striatal and bundle 6-OHDA injections. In addition, by combining pre-training with the use of a short set of holds, improved sensitivity of this task can be achieved. This improvement in sensitivity may be of advantage when exploring new therapeutic interventions for PD, where subtle but relevant changes in performance may arise.
authors.affiliation: Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales, UK. Electronic address: Hanna.Lindgren@med.lu.se.
authors.forename: Hanna S
authors.initials: HS
authors.lastname: Lindgren
authors.affiliation: Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Klein
authors.affiliation: Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales, UK.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Dunnett
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity*; D000661:Amphetamine; D000704:Analysis of Variance; D000818:Animals; D002755:Choice Behavior / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced*; D004195:Disease Models, Animal; D005260:Female; D007839:Functional Laterality / Q000187:drug effects* / Q000502:physiology; D016627:Oxidopamine / Q000633:toxicity*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011930:Reaction Time / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects / Q000293:injuries*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase
keywords: 6-OHDA; Dopamine; Operant; Parkinson's disease; Training