DIFFERENTIAL SENSITIVITY TO HYDROGEN-PEROXIDE OF DOPAMINERGIC AND NORADRENERGIC NEUROTRANSMISSION IN RAT-BRAIN SLICES

Oxidative stress, induced by hydrogen peroxide, has been implicated in the pathogenesis of Parkinson's disease. Only scarce information is available if and how hydrogen peroxide, a side product of catecholamine (CA) breakdown, interferes with CAergic neurotransmission. Therefore, we investigated the effect of hydrogen peroxide on the release of [H-3]dopamine (DA) and [H-3]noradrenaline (NA) from rat striatal and cortical tissue slices, respectively. Hydrogen peroxide (0.01-1 mM) stimulated the spontaneous release of [H-3]DA from striatal slices. Its effect on [H-3]NA release from cortical slices, however, was much smaller than on DA release and occurred only in concentrations above 0.1 mM. Furthermore, only in concentrations of 1 mM or higher did a stimulation of spontaneous release of radioactivity from striatal slices incubated with [H-3]choline occur. Omission of calcium significantly enhanced the effect on DA release, and an increase of calcium significantly reduced it. Blockade of vesicular storage with reserpine (0.3 mu M) almost completely abolished [H-3]DA release induced by hydrogen peroxide. Following incubation of striatal slices with [H-3]NA in the presence of the NA (re)uptake blocker desmethylimipramine (0.3 mu M), NA release was observed at a concentration (0.1 mM) at which no effect occurred in cortical slices. Moreover, under these conditions [(3)]NA and [H-3]DA release from striatal slices reached comparable levels. Our results show that hydrogen peroxide induces a nonexocytotic release of DA and NA by interfering with the vesicular uptake and/or storage of these CAs. However, the striatal DA storage system, irrespective of the presence of either DA or NA, appeared to be substantially more sensitive to this effect than its cortical equivalent for storage of NA.