Effects of dopamine and serotonin antagonist injections into the striatopallidal complex of asymptomatic MPTP-treated monkeys.

The cardinal symptoms of Parkinson's disease (PD), akinesia, rigidity and tremor, are only observed when the striatal level of dopamine (DA) is decreased by 60-80%. It is likely that compensatory mechanisms during the early phase of DA depletion delay the appearance of motor symptoms. In a previous study, we proposed a new PD monkey model with progressive MPTP intoxication. Monkeys developed all of the motor symptoms and then fully recovered despite a large DA cell loss in the substantia nigra (SN). Compensatory mechanisms certainly help to offset the dysfunction induced by the DA lesion, facilitating motor recovery in this model. Neurotransmitter measurements in the striatal sensorimotor and associative/limbic territories of these monkeys subsequently revealed that DA and serotonin (5-HT) could play a role in recovery mechanisms. To try to determine the involvement of these neurotransmitters in compensatory mechanisms, we performed local injections of DA and 5-HT antagonists (cis-flupenthixol and mianserin, respectively) into these two striatal territories and into the external segment of the globus pallidus (GPe). Injections were performed on monkeys that were in an asymptomatic state after motor recovery. Most parkinsonian motor symptoms reappeared in animals with DA antagonist injections either in sensorimotor, associative/limbic striatal territories or in the GPe. In contrast to the effects with DA antagonist, there were mild parkinsonian effects with 5-HT antagonist, especially after injections in sensorimotor territories of the striatum and the GPe. These results support a possible, but slight, involvement of 5-HT in compensatory mechanisms and highlight the possible participation of 5-HT in some behavioural disorders. Furthermore, these results support the notion that the residual DA in the different striatal territories and the GPe could be involved in important mechanisms of compensation in PD.