Abstract
We examined whether (-)-nicotine infusion can affect kainic acid (KA)-induced neurotoxicity in rats. Although treatment with a single nicotine infusion (0.5 or 1.0 microg/side, i.c.v.) failed to attenuate KA-induced neurotoxicity, repeated nicotine infusions (1.0 microg/side/day for 10 days) attenuated the seizures, the severe loss of cells in hippocampal regions CA1 and CA3, the increase in activator protein (AP)-1 DNA binding activity, and mortality after KA administration. alpha-Bungarotoxin and mecamylamine blocked the neuroprotective effects of nicotine. These results suggest that repeated nicotine treatment provides alpha7 nicotinic acetylcholine receptor-mediated neuroprotection against KA toxicity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bungarotoxins / pharmacology
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DNA / metabolism
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Dihydro-beta-Erythroidine / pharmacology
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Hippocampus / drug effects*
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Hippocampus / pathology
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Injections, Intraventricular
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Kainic Acid
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Kindling, Neurologic
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Male
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Mecamylamine / pharmacology
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Neuroprotective Agents / pharmacology*
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Nicotine / administration & dosage
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Nicotine / pharmacology*
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Nicotinic Antagonists / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Nicotinic / drug effects*
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Receptors, Nicotinic / metabolism
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Seizures / chemically induced
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Seizures / mortality
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Seizures / prevention & control*
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Transcription Factor AP-1 / metabolism*
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alpha7 Nicotinic Acetylcholine Receptor
Substances
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Bungarotoxins
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Chrna7 protein, rat
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Neuroprotective Agents
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Nicotinic Antagonists
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Receptors, Nicotinic
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Transcription Factor AP-1
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alpha7 Nicotinic Acetylcholine Receptor
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Dihydro-beta-Erythroidine
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Mecamylamine
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Nicotine
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DNA
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Kainic Acid