Abstract
The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes, via its metabolite MPP(+), damages of the nigrostriatal dopaminergic pathway, similar to those observed in Parkinson's disease. An intranigral injection of 10 microg MPP(+) in rat induced a decrease of about 30% of the neuronal dopamine transporter (DAT) activity 21 days after lesion. Based on the hypothesis that MPTP/MPP(+) neurotoxicity involves the nitric oxide (NO) production and/or an activation of poly(ADP-ribose) polymerase (PARP), we investigated the preventive effects of a treatment either with L-Name, a NO synthase (NOS) inhibitor or 3-aminobenzamide, a PARP inhibitor on the reduction of dopamine uptake induced by MPP(+). Rats received a daily injection i.p. of 50 mg/kg L-Name or 10 mg/kg 3-aminobenzamide 3 days before and during 21 days after the MPP(+) lesion. The results showed that inhibitors of NOS and PARP did not prevent the alteration of DAT activity induced by 10 microg MPP(+), indicating that NO and PARP were not involved in the biochemical cascade leading to the inhibition of rat DAT activity by MPP(+) in our experimental conditions.
MeSH terms
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1-Methyl-4-phenylpyridinium / pharmacology
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Animals
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Dopamine / metabolism
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Dopamine / pharmacokinetics
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Dopamine Plasma Membrane Transport Proteins
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Drug Interactions / physiology
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Enzyme Inhibitors / pharmacology*
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Male
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Membrane Glycoproteins*
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Membrane Transport Modulators*
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Membrane Transport Proteins / antagonists & inhibitors*
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Membrane Transport Proteins / metabolism
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Nerve Tissue Proteins*
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Neurons / drug effects*
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Neurons / enzymology
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Neuroprotective Agents / pharmacology
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Nitric Oxide / metabolism
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Nitric Oxide Synthase / antagonists & inhibitors*
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Nitric Oxide Synthase / metabolism
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Parkinsonian Disorders / drug therapy*
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Parkinsonian Disorders / enzymology
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Parkinsonian Disorders / physiopathology
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Poly Adenosine Diphosphate Ribose / antagonists & inhibitors*
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Poly Adenosine Diphosphate Ribose / metabolism
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism
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Radioligand Assay
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Rats
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Rats, Wistar
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Substantia Nigra / drug effects*
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Substantia Nigra / enzymology
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Substantia Nigra / physiopathology
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Synaptosomes / drug effects
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Synaptosomes / metabolism
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Tritium
Substances
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Dopamine Plasma Membrane Transport Proteins
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Enzyme Inhibitors
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Membrane Glycoproteins
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Membrane Transport Modulators
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Neuroprotective Agents
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Slc6a3 protein, rat
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Tritium
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Poly Adenosine Diphosphate Ribose
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Nitric Oxide
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Nitric Oxide Synthase
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1-Methyl-4-phenylpyridinium
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Dopamine