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Central neurotoxic effects of intraperitoneally administered 3-acetylpyridine, harmaline and niacinamide in Sprague-Dawley and Long-Evans rats: a critical review of central 3-acetylpyridine neurotoxicity.

Abstract：

:Previous studies indicate that 3-acetylpyridine (3-AP) intoxication produces discrete lesions of the inferior olive (IO) and other central structures in rats and mice. As a result, it has been widely employed in investigations of the influences of climbing fibers on cerebellar function. This study examines the central toxicity of a protocol reported to produce lesions restricted to the inferior olive in rats. Adult male Long-Evans (n = 12) and Sprague-Dawley (n = 18) were given serial injections of 3-AP (75-80 mg/kg), harmaline (15 mg/kg) or saline, and niacinamide (300 mg/kg). Silver degeneration staining (cupric-silver method) after 6-48 h survival revealed consistent patterns of degenerating neurons in IO, nucleus ambiguus, hypoglossal nucleus, dorsal motor nucleus X, nucleus intercalatus, nucleus dorsalis raphe, medial terminal nucleus, interpeduncular nucleus, substantia nigra, ventral tegmental area, entopeduncular nucleus, hippocampus (dentate gyrus and CA 3-4), horizontal limb of the nucleus of the diagonal band, and lateral entorhinal cortex, which were not produced by control experiments with 3 saline injections or with two saline injections followed by niacinamide. These data apparently resolve conflicts in the literature regarding central 3-AP toxicity and indicate that the 3-AP-harmaline-niacinamide protocol produces degeneration that is similar to 3-AP alone. However, they also document the discrete, reproducible susceptibility of certain neuronal populations to 3-AP intoxication and suggest that the motor symptoms of intoxication are not solely due to IO destruction. Finally, they form a basis for biochemical investigations of 3-AP toxicity in susceptible central structures.

journal_name

Brain Res

journal_title

Brain research

authors

Balaban CD

doi

10.1016/0165-0173(85)90017-7

subject

Has Abstract

pub_date

1985-04-01 00:00:00

pages

21-42

issue

eissn

0006-8993

issn

1872-6240

journal_volume

356

pub_type

杂志文章

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Central neurotoxic effects of intraperitoneally administered 3-acetylpyridine, harmaline and niacinamide in Sprague-Dawley and Long-Evans rats: a critical review of central 3-acetylpyridine neurotoxicity.