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Vol.43 No.5 >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/1862

Title: ニコチンによる急性毒性と加齢の影響について
Other Titles: STUDIES ON ACUTE TOXICITY OF NICOTINE AND AGING
Authors: 岡本, 雅人
Keywords: nicotin
acute toxicity
dopaminergic neurons
aging
hepatic metabolism
Issue Date: 31-Oct-1992
Publisher: 奈良医学会
Citation: 奈良医学雑誌 Vol.43 No.5 p.464-474
Abstract: The mechanisms in the brain for acute toxicity of nicotine were investigated in rats. Age-related changes in acute toxicity of nicotine were also studied. An acute intraperitoneal (i. p.) or intracerebroventricular (i. c. v.) injection of nicotine intensified convulsions and death dose-dependently. But those convulsive responses induced by nicotine (i. c. v.) were more rapid and shorter than those induced by nicotine (i. p.). Acute toxic effects of nicotine were dose-dependently antagonized by mecamylamine (i. p. or i. c. v.), but not by hexamethonium (i. p.). Nicotine (10 or 24.5 mg/kg, i. p.) significantly increased dopamine, 3, 4-dihydroxyphenylacetic acid and homovanillic acid in striatum. Furthermore, electrical lesion of striatum suppressed acute toxicities of nicotine. Pretreatment of SCH-23390, but not of haloperidol or sulpiride, blocked nicotine-induced convulsions and death. Pretreatment of phenobarbioal, diazepam or MK-801 also prevented acute toxicity of nicotine. Nicotine levels in the blood and cortex after an acute i. p. injection of nicotine (24.5 mg/kg) were significantly higher in old rats than in young rats. Hepatic metabolisms of nicotine decreased age-relatedly. Also, nicotine (24.5 mg/kg, i. p.)-induced lethality tended to increase in old rats. On the other hand, nicotine (24.5 mg/kg, i. p.) did not change monoamine levels in any brain regions in old rats. These results indicate that acute toxic effects of nicotine can be attributed to a central site. Acute toxicity of nicotine may be related to dopaminergic neurons, especially in the nigrostriatal system, as well as GABAergic and glutamatergic neurons. Furthermore, stimulation of D1 receptors in the central dopaminergic system may be concerned with the propagation of acute toxic effects of nicotine. Also, acute toxicity of nicotine in old rats may be involved in two significant decreases, in hepatic metabolism of nicotine and in brain sensitivity to nicotine.
URI: http://hdl.handle.net/10564/1862
ISSN: 04695550
13450069
Appears in Collections:Vol.43 No.5

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