Impairment of the neuronal dopamine transporter activity in MPP+-treated rat was not prevented by treatments with nitric oxide synthase or poly(ADP-ribose) polymerase inhibitors

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes, via its metabolite MPP+, damages of the nigrostriatal dopaminergic pathway, similar to those observed in Parkinson's disease. An intranigral injection of 10 mug MPP+ in rat induced a decrease of about 30% of the neuronal dopa mine transporter (DAT) activity 21 days after lesion. Based on the hypothes is that MPTP/MPP+ neurotoxicity involves the nitric oxide (NO) production a nd/or an activation of poly(ADP-ribose) polymerase (PARP), we investigated the preventive effects of a treatment either with L-Name, a NO synthase (NO S) inhibitor or 3-aminobenzamide, a PARP inhibitor on the reduction of dopa mine uptake induced by MPP+. Rats received a daily injection i.p. of 50 mg/ kg L-Name or 10 mg/kg 3-aminobenzamide 3 days before and during 21 days aft er the MPP+ lesion. The results showed that inhibitors of NOS and PARP did not prevent the alteration of DAT activity induced by 10 mug MPP+, indicati ng that NO and PARP were not involved in the biochemical cascade leading to the inhibition of rat DAT activity by MPP+ in our experimental conditions. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.