Study and knowledge on the relationship between dopamine increase in the middle brain and Parkinson's disease

Parkinson's disease is caused by a loss of nerve cells in part of the brain called the substantia nigra. This leads to a reduction in a chemical called dopamine in the brain. Dopamine plays a vital role in regulating the movement of the body. A reduction in dopamine is responsible for many of the symptoms of Parkinson's disease. Exactly what causes the loss of nerve cells is unclear. Most experts think that a combination of genetic and environmental factors is responsible. Parkinson's disease is a brain disorder that causes unintended or uncontrollable movements, such as shaking, stiffness, and difficulty with balance and coordination. Symptoms usually begin gradually and worsen over time. As the disease progresses, people may have difficulty walking and talking. Dopamine is a chemical released in the brain that makes you feel good. Having the right amount of dopamine is important both for your body and your brain. Dopamine helps nerve cells to send messages to each other. Peak-dose dyskinesias are abnormal movements that usually occur ۱ h after oral administration of levodopa, and often complicate chronic treatment of Parkinson's disease. We investigated by PET with [۱۱C]raclopride whether Parkinson's disease progression modifies the striatal changes in synaptic dopamine levels induced by levodopa administration, and whether this modification, if present, could have an impact on the emergence of dyskinesias. We found that, ۱ h after oral administration of standard-release ۲۵۰/۲۵ mg of levodopa/carbidopa, levodopa-induced increases in synaptic dopamine levels (as estimated by striatal changes in [۱۱C]raclopride binding potential) correlated positively with duration of Parkinson's disease symptoms (for the caudate nucleus, r = ۰.۷۹, P < ۰.۰۰۱; for the putamen, r = ۰.۸۸, P < ۰.۰۰۰۱). Patients with peak-dose dyskinesias had larger ۱-h increases in synaptic dopamine levels than stable responders, but there were no between-group differences in [۱۱C]raclopride binding ۴ h post-levodopa. The corresponding (time × group) interaction term in the repeated measures analysis of covariance was significant, even after adjusting for between-group differences in duration of Parkinson's disease symptoms (for the caudate nucleus, P = ۰.۰۳۰; for the putamen, P = ۰.۰۲۱). Our results indicate that, at the synaptic level, an identical dose of levodopa induces increasingly larger ۱-h changes in dopamine levels as Parkinson's disease progresses. Large levodopa-induced increases in synaptic dopamine concentration can lead to dramatic changes in receptor occupancy, which may be responsible for the emergence of peak-dose dyskinesias in Parkinson's disease.

کلیدواژه ها:

dopamine release ، dyskinesias ، Parkinson's disease ، PET ، raclopride