Apornorphine offers new insight into dopaminergic neuron vulnerability in mesencephalic cultures

The mechanism by which the dopamine neurons of the substantia nigra pars compacta degenerate in Parkinson's disease, is partly unknown. Dopamine could be implicated in this phenomenon, and in order to explain its toxicity several hypotheses have been suggested. The similarity between apomorphine and dopamine as regards their chemical, pharmacological and toxicological properties provided a basis for investigating the nature of the toxicity of the former agent. In this study we describe some effects of apomorphine on mouse mesencephalic cell cultures at relatively low concentrations (from 0.5 to 2.5 mu M), apomorphine produced a neurotrophic effect, consisting of a 60% increase in dopaminergic neuron survival as measured by 13 HI dopamine uptake. At high concentrations (over 20 mu M), however, apomorphine induced an increasing cytotoxic effects as measured by the marked decrease in [H-3] dopamine uptake, and by the direct observation of the dopaminergic neurons after TH immunostaining. This study may offer a new strategy for investigating the mechanisms underlying DA neuron vulnerability. (c) 2008 Elsevier Ltd. All rights reserved.