Increased striatal neuropeptide Y immunoreactivity and its modulation by deprenyl, clonidine and L-dopa in MPTP-treated mice.

The aim of this study was to evaluate the effect of MPTP (2 x 45 mg/kg s.c., 20 h apart) on striatal neuropeptide Y-like immunoreactivity (NPY-LI) in C57BL/6 mice. NPY-LI markedly increased 2 weeks after MPTP but it remained unchanged after 24 h, 1 or 6 weeks. The increase in NPY-LI was accompanied by depletion of dopamine (-80%), DOPAC (-70%), 3-MT (-44%) and HVA (-52%). L-Deprenyl completely prevented the MPTP-induced NPY-LI increase, neurodegeneration of the striatal dopamine system and motor dysfunction. Clonidine attenuated the neurotoxin effect on NPY-LI and dopaminergic neurons. L-dopa/carbidopa protected NPY neurons against MPTP but slightly enhanced MPTP-induced decrease in the levels of dopamine and its metabolites. The relationship between changes in NPY-LI and dopamine and serotonin metabolism determined by HPLC was discussed. The results further extend the range of MPTP-elicited modifications in striatum and demonstrate that drugs with antiparkinsonian activity can protect NPY neurons against MPTP toxicity.