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We previously demonstrated that lobeline effectively inhibited dopamine transporter (DAT)-mediated dopamine (DA) transportation. Therefore, the present study aimed to investigate whether lobeline shows protective effects against neurotoxin-induced cell death in vivo. Mice were administered 30 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) and treated with 80 mg/kg L-dopa, 10 mg/kg GBR12935 or 1 or 3 mg/kg lobeline, respectively, via injection. Rotarod and swim tests as well as tyrosine hydroxylase (TH) immunohistochemistry were carried out to evaluate the effects of these drugs. Compared with L-DA and GBR12935, lobeline (3 mg/kg administered via intraperitoneal injection) on behavior and dopaminergic neurons. Compared with L-DA and GBR12935, lobeline (3 mg/kg injected subcutaneously) significantly reduced MPTP induced locomotive deficits detected in behavioral tests. In addition, TH immunostaining showed that lobeline (3 mg/kg) markedly decreased the neurotoxin-induced immunoreactivity loss in the substantia nigra and striatum. Lobeline may be useful in the protection of dopaminergic neurons and may alleviate the symptoms of Parkinson's disease.
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