3-Acetylpyridine neurotoxicity to the nigrostriatal dopamine system in mice

Employing tyrosine hydroxylase (TH) immunohistochemistry, the neurotoxic effects of 3-acetylpyridine (3-AP), a potent neurotoxin selective to olivocerebellar climbing fibers, on the mesencephalic dopamine systems were investigated in mice. Systemic injections of 3-AP resulted in a large loss of TH-immunoreactive nigrostriatal neurons. On the other hand, 3-AP neurotoxicity to the mesolimbic dopamine system was much less drastic. The 3-AP-induced concurrent loss of olivocerebellar and nigrostriatal neurons may replicate an essential neuropathological feature of olivopontocerebellar atrophy-associated parkinsonism.