The validity of the pre-treated, unilaterally MPTP-treated monkey as model of Parkinson's disease: a detailed behavioural analysis of the therapeutic and undesired effects of the D2 agonist LY 171555 and the D1 agonist SKF 81927.
SourceBehavioural Pharmacology, 10, 2, (1999), pp. 163-173
Article / Letter to editor
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SubjectFunction and dysfunction of the basal ganglia: the MPTP-monkey and Parkinson's disease; Pathophysiology of Brain and Behaviour; Functies en disfuncties van de basale ganglia, i.h.b. m.b.t. de ziekte van Parkinson: het MPTP-model; Pathofysiologie van Hersenen en Gedrag
The goal of this study was to evaluate the validity of the pretreated, unilaterally MPTP-treated monkey as an animal model of Parkinson's disaese (PD). For that purpose, a detailed ethogram was developed and assessed in in four male rhesus monkeys that had received MPTP (2.5) mg) in the carotid artery contralateral to the dominant limb. Subsequently, the behavioural effects of the dopamine D2 agonist quinpirole and the dopamine D1 agonist SKF 81297 were studied. The ethogram was found to allow a clear-cut and objective separation of drug-induced behaviours into therapeutic and undesired effects in the MPTP-treated monkeys. Saline-treated monkeys predominantly displayed ipsilateral goal-directed fore-limb movements, and distinct types of ipsilaterally directed rotations. Although quinpirole and SKF 81297 increased motor behaviours, such as body displacement, contralateral fore-limb movements and contralateral rotational behaviours, assessment of the new detailed ethogram revealed that this increase was completely due to the activation of abnormal, non-goal-directed behaviours, such as dyskinetic fore-limb movements, pivoting and shuffling. Moreover, the new ethogram made clear that the drug treatments induced not only dyskinesia and dystonia, but also epileptoid behaviour, which was confirmed by EEG analysis. In summary, the detailed behavioural analysis showed that this model does not adequately predict the clinical effects of the D2 agonist. It is concluded that the pretreated, unilaterally MPTP-treated monkey is not a valid model to predict the therapeutic und undesired effects of dopaminergic drugs in humans.
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