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Epidemiological studies of Parkinson disease (PD) have found an inverse correlation between cigarette smoking and the risk of developing PD, which suggests that nicotine has a protective effect. Results from animal models of PD are conflicting, raising questions about a protective potential of nicotine. In this study, mice were pretreated with low-dose nicotine before MPTP administration, and examined to determine a neuroprotective potential of nicotine. The schedule of nicotine administration was selected to simulate the future human trials using this putative neuroprotective agent. Male C57Bl/6 mice were pretreated with nicotine for 5 days (0.2 mg/kg/d, i.p.). After the 5-day-pretreatment with nicotine only, nicotine and MPTP (30 mg/kg/d, i.p.) were co-administered for 1 to 5 consecutive days. The total dose of nicotine, 0.2 mg/kg/d for 6 to 10 days, is the lowest one ever studied. Tyrosine hydroxylase (TH) immunohistochemical staining of the nigral sections was performed. Over the experimental period, there was a significant reduction in the TH-positive cells. In the nicotine-MPTP group, the degree of TH neuron depletion was reduced at days 4 and 5 of co-administration. These findings suggest that the nicotinic neurotransmission on the dopaminergic neurons are promising targets for neuroprotective therapy of PD.
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