Pergolide protects dopaminergic neurons in primary culture under stress conditions

Summary.

Dopamine agonists are an important therapeutic strategy in the treatment of Parkinson's disease. They postpone the necessity for and reduce the required dose of L-3,4-dihydroxyphenylalanine (L-DOPA) medication thus protecting against the development of motor complications and potential oxidative stress due to L-DOPA metabolism. In primary cultures from mouse mesencephalon we show that pergolide, a preferential D₂ agonist enhanced the survival of healthy dopaminergic neurons at low concentrations of 0.001 μM. About 100 fold higher concentrations (0.1 μM) were necessary to partially reverse the toxic effects of 10 μM 1-methyl-4-phenylpyridinium (MPP⁺). Pergolide was equally effective in preventing the reduction of dopamine uptake induced by 200 μM L-DOPA. Furthermore, between 0.001–0.1 μM it also reduced lactate production thus promoting aerobic metabolism. The present findings suggest that pergolide protects dopaminergic neurons under conditions of elevated oxidative stress.