Comparison of 6-hydroxydopamine lesions of the substantia nigra and the medial forebrain bundle on a lateralised choice reaction time task in mice.

Parkinson's disease is most commonly modelled via unilateral infusion of the neurotoxin 6-hydroxydopamine (6-OHDA) in the rat, but recent work has been aimed to translate the reproducibility and reliability of the model to the mouse. Here we present the effects of unilateral 6-OHDA lesions to either the medial forebrain bundle or the substantia nigra (SN) in mice, which were trained on a lateralised choice reaction time (RT) task. This task measures response accuracy as well as RT and movement time latencies, and offers the opportunity for a more fine-grained analysis of the precise nature of the movement deficit, motor learning and functional recovery than can be achieved using classical tests of simple motor asymmetry. Both lesion types caused impaired response accuracy, which was more pronounced when responses had to be directed contralateral to the lesion. Furthermore, movement times were increased for both lesion groups, whereas only the bundle lesion group displayed a RT deficit. The lesions were stable over three consecutive weeks of testing, therefore lesion-type and behavioural assessment on the operant task are suitable to investigate the dopaminergic system in parkinsonian mice. Both lesions were stable over time, and were more pronounced when responses were directed in contralateral space; the mice with more complete bundle lesions displayed a greater deficit than mice that received lesions to the SN. The translation of this choice RT task will be beneficial for the assessment of therapeutics in mouse models of the disease.