Presynaptic involvement in the nicotine prevention of the dopamine loss provoked by 6-OHDA administration in the substantia nigra

被引:0
作者
J. Andrés Abin-Carriquiry
Ronald McGregor-Armas
Gustavo Costa
Jessika Urbanavicius
Federico Dajas
机构
[1] Instituto de Investigaciones Biológicas Clemente Estable,Department of Neurochemistry
来源
Neurotoxicity Research | 2002年 / 4卷
关键词
Corpus striatum; Microdialysis; Nicotine; Substantia nigra; Extracellular dopamine; Parkinson’s disease; 6-Hydroxydopamine;
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学科分类号
摘要
While nicotine, through stimulation of a specific sub population of nicotinic acetylcholine receptors (nAChR) appears to protect cells in culture against a variety of insults, studies in vivo show controversial results. In a previous paper we have shown that in the 6-hydroxydopamine (6-OHDA) model of experimental parkinsonism, an intermittent administration schedule of nicotine (4h before and 20, 44 and 68h after 6-OHDA) was able to prevent the decrease of dopamine (DA) concentration in the corpus striatum (CS) provoked by the partial lesion of the substantia nigra (50% neuronal death after 6 μg of 6-OHDA). To further analyze the mechanisms of nicotine effects, we performed a microdialysis study of striatal extracellular DA concentrations utilizing the nicotine administration schedule that was able to prevent DA decrease. Basal extracellular DA concentrations in the CS were maintained after 6-OHDA and were not modified by nicotine. Basal DOPAC levels were decreased after the neurotoxic administration. The response of extracellular DA to potassium chloride (KCl) challenge was significantly lower after 6-OHDA than in control animals. Nicotine significantly reversed this decrease. As previous studies have shown, the striatal DA terminals surviving the 6-OHDA toxic effect are able to keep extracellular DA concentrations close to normal, likely increasing DA synthesis. Nevertheless, the application of a releasing factor such as KCl shows the fragility of this equilibrium, exposing a decrease in the terminal number. Nicotine, through a further activation of tyrosine hydroxylase and DA synthesis or by prolonging the life of DA terminals, could reverse the effect of 6-OHDA.
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页码:133 / 139
页数:6
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  • [1] Akaike A.(1994)Nicotine-induced protection of cultured cortical neurons against J. Brain Res. 644 181-187
  • [2] Tamura Y.(1992)-methyl- J. Neurochem. 52 776-779
  • [3] Yokota T.(1994)-aspartate receptor-mediated glutamate cytotoxicity Brain Res. 662 11-24
  • [4] Shimohama S.A.(1996)Nicotine enhances 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity Neuroscience 70 169-177
  • [5] Kimura J.(1998)Evidence for volume transmission in the dopamine denervated neostriatum of the rat after a unilateral nigral 6-OHDA microinjection. Studies with systemic J. Neurobiol. 35 29-36
  • [6] Behmand R.A.(1990)-amphetamine treatment Brain Res. 508 30-39
  • [7] Harik S.I.(1990)Chronic continuous infusion of (−) nicotine reduces basic fibroblast growth factor messenger RNA levels in the ventral midbrain of the intact but not of the 6-hydroxydopamine-lesioned rat J. Neurosci. 10 1847-1854
  • [8] Bjelke B.(2001)Nicotine blocks TNF-alpha-mediated neuroprotection to NMDA by an alpha-bungarotoxin-sensitive pathway Brain Res. 888 336-342
  • [9] Stromberg I.(1998)Dopamine depletion in neonatal rats: effects on behavior and striatal dopamine release assessed by intracerebral microdyalisis during adulthood Neuroscience 87 63-78
  • [10] O’Connor W.T.(2000)Changes in striatal dopamine neurotransmission assessed with microdialysis following recovery from a bilateral 6-OHDA, lesion: variation as function of lesion size Neuropharmacology 39 2799-2807