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.

Dysfunction of the subthalamic nucleus induces behavioral and movement disorders in monkeys.

High-frequency stimulation of the subthalamic nucleus (STN) in parkinsonian patients is reported to induce psychiatric effects. The likely explanation for these effects is the partitioning of the STN into sensorimotor, associative, and limbic anatomo-functional territories. Thus, a specific neuronal dysfunction of the STN sensorimotor territory could lead to abnormal movements, whereas a dysfunction of the associative or limbic territory could lead to behavioral disturbances.

Behavioral and movement disorders induced by local inhibitory dysfunction in primate striatum.

The current model of basal ganglia organization postulates their functional division into sensorimotor, associative, and limbic territories, implicated, respectively, in motor, cognitive, and motivational aspects of behavior. Based on this model, we previously demonstrated, in the external segment of globus pallidus of monkeys, that the same neuronal dysfunction induced dyskinesia or abnormal behavior depending on the functional territory. To extend these findings, we performed bicuculline microinjections into the different functional territories of the striatum in 6 monkeys.

Behavioral recovery in MPTP-treated monkeys: neurochemical mechanisms studied by intrastriatal microdialysis.

Parkinson's disease (PD) patients express motor symptoms only after 60-80% striatal dopamine (DA) depletion. The presymptomatic phase of the disease may be sustained by biochemical modifications within the striatum. We used an appropriate specific 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model (Mounayar et al.

High-frequency stimulation of the anterior subthalamic nucleus reduces stereotyped behaviors in primates.

Growing evidence shows that dysfunction of the limbic basal ganglia (BG) network is implicated in repetitive behaviors, such as obsessive compulsive disorder (OCD) and Tourette's syndrome (TS), in humans. Because deep brain stimulation (DBS) of the posterior subthalamic nucleus (STN), which modulates the sensorimotor BG network, is beneficial in movement disorders, stimulation of the anterior, limbic STN might improve intractable behavioral disorders. We therefore evaluated the effect of anterior STN stimulation on the repetitive behaviors induced in two monkeys after bicuculline-induced dysfunction of the limbic external globus pallidus.

A new model to study compensatory mechanisms in MPTP-treated monkeys exhibiting recovery.

The cardinal symptoms in Parkinson's disease (PD), akinesia, rigidity and tremor, are only observed when the striatal level of dopamine is decreased by 60-80%. During the preclinical phase of PD, compensatory mechanisms are probably involved in delaying the appearance of motor symptoms. In a MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of PD, a spontaneous recovery has been reported after initial intoxication suggesting that compensatory mechanisms are activated in this model as well.