neuroprotective effect of the systemic administration of mk-801 on the pedunculopontine nucleus of hemiparkinsonian rats

Glutamatergic antagonists were administered in rats, as part of the current pharmacological therapies for neuroprotection of patients with Parkinson disease, due to glutamatergic hyperactivity and the deleterious effects of this condition. The effect of the systemic administration of MK-801, an antagonist of N-methyl-D-aspartate (NMDA) receptors, was evaluated on the extracellular concentrations of glutamate (Glu) and gamma amino butyric acid (GABA), loss of dopaminergic cells and cell death in the pedunculopontine nucleus (PPN) of hemiparkinsonian rats. Five treatments were studied in Wistar rats: lesion in the substantia nigra pars compacta (SNpc) with 6- hydroxydopamine (6-OHDA)(n = 15); 6-OHDA lesion plus the systemic administration of MK-801 (0.5 mg/kg; n = 17); false lesion in the SNpc (n = 10), false lesion in the SNpc plus false systemic treatment (n = 10) and no treatment (n = 22). The extracellular concentrations of Glu and GABA were analyzed by cerebral microdialysis and high performance liquid chromatography coupled to fluorometric detection. The loss of dopaminergic cells and cell death processes in the PPN were assessed by immunohistochemistry for tyrosine hydroxylase and the TUNEL technique, respectively. The extracellular concentrations of Glu and GABA significantly decreased in the PPN after the MK-801 treatment, compared to untreated hemiparkinsonian rats. This treatment caused a decreased loss of dopaminergic cellular bodies in the tegmental ventral area of rats and prevented cell death in the PPN of hemiparkinsonian rats. These results suggest a neuroprotective effect mediated by a decreased glutamatergic tone in hemiparkinsoninan rats systemically treated with an antagonist of NMDA receptors.