Chronic Nicotine Treatment Differentially Regulates Substance P and Tyrosine Hydroxylase Immunoreactivity in Substantia Nigra Ipsilateral to a Unilateral Lesion

The present study was carried out with a variety of neuroanatomical techniques to investigate the consequences of chronic continuous nicotine treatment (0.125 mg · kg⁻¹ · h⁻¹, sc, 14 days) on the lesion-induced effects of a partial meso-diencephalic hemitransection. Both the striatonigral substance P (SP) and the nigrostriatal dopamine (DA) pathways were studied. The lesion-induced degenerative changes were most pronounced in the lateral parts of the ipsilateral substantia nigra and striatum. We have previously demonstrated that chronic nicotine infusion counteracts the lesion-induced loss of nigral tyrosine hydroxylase (TH) immunoreactive/Nissl stained DA neurons. The main finding of this study is that this phenomenon also involves changes in the striatonigral pathways. Thus, nicotine induced a disappearance of SP immunoreactive nerve terminals in substantia nigra pars compacta on the lesioned side, while it was again shown to counteract the lesion-induced disappearance of nigral TH immunoreactivity in the same animals. These data are interpreted on the basis of previous electrophysiological findings, where nicotine under similar experimental conditions counteracted the lesion-induced increase in burst firingin vivoin nigral dopamine neurons. Taken together these results indicate that nicotine may act by a reduced SP excitatory input to the nigral DA cells, which rescues them from dying. It is likely that the surviving cells are functional, since increased extracellular striatal DA levels have been observed after nicotine treatment ipsilateral to the lesion in a previous microdialysis experimentin vivo.These findings might contribute to the development of new neuroprotective therapies for patients suffering from neurodegenerative disorders such as Parkinson's disease.