Lobeline shows protective effects against MPTP-induced dopaminergic neuron death and attenuates behavior deficits in animals

Abstract

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.