Nicotine and Animal Models of Parkinson’s Disease

The effect of chronic continuous (-)nicotine treatment in lesioned nigrostriatal dopamine (DA) systems was studied in rats with a partial unilateral mesodiencephalic lesion. (-)Nicotine significantly counteracted both the lesion-induced reduction in total number of nigral tyrosine-hydroxylase-like (TH-li) immunoreactive neurons and the lesion-induced upregulation of the high-affinity binding sites of the striatal DA D2 receptors analyzed with [3H]N-propylnorapomorphine. The suggested mechanism for the neuroprotection is a functional desensitization of the nicotinic cholinoceptors located on DA nerve cells. In a different lesion model, (-)nicotine either attenuated or enhanced 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice depending on the dose-schedule. Here, we suggest an action of MPTP on the nicotinic cholinoceptors preventing functional desensitization from taking place.