title: Interactive Effects of Nicotine and MPTP on Striatal Tetrahydrobiopterin in Mice.
abstract: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin known to cause dopamine (DA) neuron degeneration, while the psychoactive compound nicotine is known to excite DA neurons. Tetrahydrobiopterin is the cofactor for tyrosine hydroxylase (TOH) in the regulation of DA biosynthesis. The present study investigated the interactions between nicotine and MPTP on striatal biopterin, DA and TOH activity in BALB/c mice. The results indicated that both acute and chronic nicotine administrations at various concentrations significantly increased biopterin and DA levels in the striatum, while MPTP markedly decreased these measures. Pretreatment with nicotine at a dose having no significant effect alone, partially protected against MPTP's toxicity on biopterin and DA. Increasing the dose of nicotine did not have a further protective action. The toxicity of MPTP on TOH was also prevented by nicotine. Further, the above effects of nicotine were probably mediated through the cholinergic nicotinic receptors since mecamylamine reversed the effects of nicotine. These results suggest that nicotine interacts with the dopaminergic system probably at the level of DA biosynthesis through activating TOH and its coenzyme tetrahydrobiopterin. Copyright 1996 S. Karger AG, Basel
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: M.J.
authors.initials: MJ
authors.lastname: Tsai
authors.forename: H.L.
authors.initials: HL
authors.lastname: Wang
authors.forename: E.H.Y.
authors.initials: EH
authors.lastname: Lee