The validity of the pretreated, unilaterally MPTP-treated monkey as a model of Parkinson's disease: a detailed behavioural analysis of the therapeutic and undesired effects of the D2 agonist quinpirole and the D1 agonist SKF81297

The goal of this study was to evaluate the validity of the pretreated, unil aterally MPTP treated monkey as an animal model of Parkinson's disease (PD) . For that purpose, a detailed ethogram was developed and assessed in four male rhesus monkeys that had received MPTP (2.5 mg) in the carotid artery c ontralateral to the dominant limb. Subsequently, the behavioural effects of the dopamine D2 agonist quinpirole and the dopamine D1 agonist SKF 81297 w ere studied. The ethogram was found to allow a clear-cut and objective sepa ration of drug-induced behaviours into therapeutic and undesired effects in the MPTP-treated monkeys. Saline-treated monkeys predominantly displayed i psilateral goal-directed fore-limb movements, and distinct types of ipsilat erally directed rotations. Although quinpirole and SKF 81297 increased moto r behaviours, such as body displacement, contralateral fore-limb movements and contralateral rotational behaviours, assessment of the new detailed eth ogram revealed that this increase was completely due to the activation of a bnormal, non-goal-directed behaviours, such as dyskinetic fore-limb movemen ts, pivoting and shuffling. Moreover, the new ethogram made clear that the drug treatments induced not only dyskinesia and dystonia, but also epilepto id behaviour, which was confirmed by EEG analysis. In summary, the detailed behavioural analysis showed that this model does not adequately predict th e clinical effects of the D2 agonist. It is concluded that the pretreated, unilaterally MPTP-treated monkey is not a valid model to predict the therap eutic and undesired effects of dopaminergic drugs in humans. (C) 1999 Lippi ncott Williams & Wilkins.