Dopa-induced blood flow responses in nonhuman primates

Initially, treatment with the dopamine precursor levodopa provides substant ial symptomatic relief for patients with Parkinson's disease (PD). However, as the disease progresses, side effects such as involuntary movements or p sychosis may accompany the response to medication. The mechanisms underlyin g these actions of levodopa remain unclear. To develop methodology for long itudinal studies of the effects of PD and levodopa treatment in living nonh uman primates, we first studied the effects of an acute dose of levodopa on regional brain activity in sedated baboons using positron emission tomogra phy. We found that levodopa significantly decreased regional cerebral blood flow (rCBF) bilaterally in putamen and right cingulate and increased rCBF in right lateral temporal cortex and bilateral frontal cortex. We then perf ormed similar studies on a nemestrina in awake and sedated states to determ ine whether these responses were affected by sedation. Interestingly, the d irections of the rCBF responses in the putamen and temporal cortex were rev ersed depending on the presence or absence of sedation. Specifically, respo nses were decreased in sedated animals, but increased dose-dependently in t he awake nemestrina. These findings have important implications for the int erpretation of studies that use anesthesia. The responses in the awake neme strina were most similar to those reported in humans and thus may be the mo st useful model system. Future imaging studies using selective dopaminergic agents in awake animals may permit the identification of relatively specif ic agonist-mediated pathways and may help separate the mechanisms that medi ate levodopa's benefit from those that produce its unwanted side effects. ( C) 2000 Academic Press.