EN
An underlying mechanism of degeneration in Parkinson’s disease (PD) is unknown. The animal models of PD, developed so far have certain disadvantages; hence a search for a new model of PD seems necessary. Chronic, unilateral, intraventricular delivery of MPP+ (0.284 and 0.428 mg/kg/day for 28 days) using an ALZET osmotic minipump, implanted s.c., produced a marked, dose-dependent loss of DA and its metabolites DOPAC and HVA (50–90%) in the striatum, ipsilateral to the infusion site. DA concentration was normal in the non-infused, right striatum. Also no changes in the 5-HT level were observed. The stereological counting of the number of dopaminergic neurons in the substantia nigra pars compacta (SNc), stained with the antibody against tyrosine hydroxylase, showed their 30–50% loss on the lesioned side. Those changes were accompanied with a diminished expression of mRNA for the dopamine transporter in the SNc (by ca. 30%). Additionally, in situ hybridization studies indicated an enhanced expression of mRNA for both adenosine A2A and dopamine D2 receptors in the striatum and diminished expression of mRNA for BDNF in the hippocampus. The obtained results showed that this chronic model of continuous, intracerebral infusion of MPP+ , produced a selective nigrostriatal DA cell loss and number of other neurochemical changes resembling PD. Study supported by the grant No. NN401 1137 33 (MS&HE) and by a statutory fund from the Institute of Pharmacology, PAS, Poland.