Beyond
dopamine (DA) loss,
Parkinson's disease is associated with many other monoamine alterations. While some monoaminergic systems benefit from
l-3,4-dihydroxyphenylalanine (
l-Dopa) treatment, others seem to be further altered, contributing to
dyskinesia and nonmotor symptoms. Surprisingly, the different contributions of
parkinsonism and
l-Dopa treatment on monoaminergic changes remain largely unknown. Here, both the consequences of vehicle or
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (
MPTP) exposure and the subsequent effects of acute or chronic
l-Dopa treatment were evaluated in macaques. Monoamine levels were measured in the putamen, the motor and prefrontal cortices, the hippocampus, and the amygdala using postmortem high-pressure liquid chromatography. In normal monkeys,
l-Dopa treatment increased DA in the prefrontal cortex and hippocampus, but decreased
serotonin levels in motor domains. Chronic
l-Dopa treatment elevated monoamine levels in the prefrontal cortex, hippocampus, and amygdala in both normal and
MPTP-treated monkeys. A substantial increase in DA levels in these regions, paralleled by a decrease in
serotonin concentrations were related with
dyskinesia severity, demonstrating that major changes in monoamine release also occur in nonmotor regions. Such monoaminergic dysregulation in limbic domains may also directly contribute to the expression of motor complications, such as
dyskinesia, by impairing integrative processes upstream from motor execution.