PRESYNAPTIC AND POSTSYNAPTIC NEUROTOXIC EFFECTS OF DOPAMINE DEMONSTRATED BY INTRASTRIATAL INJECTION

被引:191
作者
FILLOUX, F
TOWNSEND, JJ
机构
[1] UNIV UTAH,SCH MED,DEPT PEDIAT,SALT LAKE CITY,UT 84132
[2] UNIV UTAH,SCH MED,DEPT PSYCHIAT,SALT LAKE CITY,UT 84132
[3] UNIV UTAH,SCH MED,DEPT PATHOL,SALT LAKE CITY,UT 84132
关键词
D O I
10.1006/exnr.1993.1008
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Considerable evidence indicates that dopamine (DA) may play a neurotoxic role in brain in certain pathologic circumstances. To investigate this issue, dopamine (1000 nmol/1 μl) was directly injected into the striatum of anesthetized Sprague-Dawley rats. Control animals received equal-volume injections of γ-aminobutyric acid (GABA) or NaCl at identical concentrations (diluted in distilled H2O, pH 7.0-7.7). Brains were removed 7 to 9 days later and frozen or fixed and sectioned for histologic and autoradiographic analysis. Dopamine injection resulted in a small-volume (3.3-mm3) lesion in comparison to control GABA and NaCl injections which produced only a needle track <0.6 mm3 in volume (P < 0.01). Dose dependency of DA toxicity was demonstrated, with substantial parenchymal damage requiring an injection of 500 nmol/1 μl. Within the lesion, marked neuronal loss, macrophage invasion, and capillary and glial proliferation were present. Acetylcholinesterase staining and D1 receptor binding were markedly reduced as well. [3H]RO5-4864 binding to peripheral benzodiazepine receptors (on astrocytes) was increased in the periphery of the lesion. The binding of 1-[3H]benzo[b]cyclohexylthiophenylpiperidine to dopamine uptake sites was also reduced, but over a wider striatal area in comparison to local parenchymal damage. Prior interruption of the dopaminergic nigrostriatal pathway (by injection of 6-hydroxydopamine) appeared to potentiate the toxicity of intrastriatal dopamine injection. The findings indicate that local injection of dopamine produces both post- and presynaptic damage to nigrostriatal structures, and support the contention that dopamine may act as a low-potency neurotoxin. © 1993 by Academic Press, Inc.
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页码:79 / 88
页数:10
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