| Abstract: | Attempting to clarify the mechanism by which intracerabral injection of 6-hydroxydopamine (60HDA) reduces catecholamines in the caudate nucleus (CN), we have tested two hypotheses: (1) 60HDA specifically attacks catecholaminergic neurons; (2) 60HDA liberates hydrogen peroxide (H2O2) which destroys neurons indiscriminately. To this end, we have injected high or low doses of 60HDA or equimolar amounts of H2O2 stereotaxically into the substantia nigra (SN) or the lateral ventricle of cats and have placed electrocoagulative lesions in the SN. We determined the CN levels of dopamine (DA), norepinephrine (NE) and serotonin (5HT) 7-10 days later. Nigral injections of high doses (8 μ mol) of either agent or low doses (80 nmol) of 60HDA decreased both DA and NE and induced similar histologic damage in the SN with neuronal drop-out at the periphery of the lesions. Injection of 80 nmol of H2O2 into the SN did not decrease CN amine levels and did not produce histologic damage in the SN. Electrocoagulation of the SN decreased CN DA and NE, but the histologic lesions failed to show any peripheral neuronal drop-out. Ventricular injections of high doses (16 μmol) of 60HDA or H2O2 reduced not only DA and NE but also 5HT levels in the ipsilateral CN. Low intraventricular doses (0-16 μmol) of 60HDA decreased only DA and NE without affecting 5HT levels in the CN whereas 0.16 μmol of H2O2 had no effect on any of the CN amines. The catecholamine-depleting effects of low doses (80 nmol) of 60HDA were significantly potentiated by inhibiting brain monoamine oxidase by 90 percent or more at the time and site of injection of 60HDA. These results suggest that the extracellular liberation of H2O2 from 60HDA could explain some possibly nonspecific effects of high doses of 60HDA; at lower doses, however, 60HDA may act via selective uptake into catecholaminergic neurons with subsequent intracellular release of H2O2. |
