3-Acetylpyridine-induced degeneration of the nigrostriatal dopamine system: an animal model of olivopontocerebellar atrophy-associated parkinsonism.

Abstract

The effects of 3-acetylpyridine (3-AP) administration to rats on the mesotelencephalic dopamine system were assessed. A single 3-AP injection resulted in biochemical and immunohistochemical evidence of degeneration of the nigrostriatal dopamine system. Six weeks after 3-AP treatment decreases in both striatal dopamine content and the activity of the catecholamine biosynthetic enzyme tyrosine hydroxylase were observed. Immunohistochemical examination suggested a decreased density of striatal tyrosine hydroxylase-immunoreactive fibers and revealed the emergence of a distinctly patchy organization of the dopamine innervation to the dorsolateral striatum. While 3-AP administration resulted in biochemical and anatomical data consistent with the degeneration of nigrostriatal dopamine fibers, no significant changes in dopamine content or the density or pattern of tyrosine hydroxylase-immunoreactive fibers in the anteromedial prefrontal cortex or nucleus accumbens were seen. These data suggest that 3-AP administration may result in a relatively specific degeneration of the nigrostriatal dopamine system. Since 3-AP causes both a profound loss of the climbing fiber input to the cerebellum derived from the inferior olivary nucleus, and the degeneration of nigrostriatal dopamine neurons, 3-AP administration may provide a useful model of olivopontocerebellar atrophy-associated parkinsonism. Moreover, the differences in the neurotoxicity caused by 3-AP and that elicited by another pyridine which causes striatal dopamine depletion (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP) may offer important insights into the mechanisms of both species- and site-specific pyridine neurotoxins.

• Authors: A Y Deutch, D L Rosin, M Goldstein, R H Roth
• Journal: Experimental neurology (Exp Neurol) Vol. 105 Issue 1 Pg. 1-9 (Jul 1989) ISSN: 0014-4886 [Print] United States
• PMID: 2568269 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Pyridines
• 3-acetylpyridine
• Tyrosine 3-Monooxygenase
• Dopamine

Topics

• Animals
• Corpus Striatum (drug effects, enzymology, metabolism)
• Dopamine (metabolism)
• Immunohistochemistry
• Male
• Nerve Degeneration
• Olivopontocerebellar Atrophies (complications)
• Parkinson Disease (complications)
• Pyridines (pharmacology)
• Rats
• Rats, Inbred Strains
• Spinocerebellar Degenerations (complications)
• Substantia Nigra (drug effects, enzymology, metabolism)
• Tyrosine 3-Monooxygenase (metabolism)