NICOTINE PREVENTS EXPERIMENTAL PARKINSONISM IN RODENTS AND INDUCES STRIATAL INCREASE OF NEUROTROPHIC FACTORS

The repeated finding of an apparent protective effect of cigarette smo king on the risk of Parkinson's disease is one of the few consistent r esults in the epidemiology of this disorder. Among the numerous substa nces that originate from tobacco smoke, nicotine is by far the most wi dely studied. Nicotine is a natural alkaloid that has considerable sti mulatory effects on the CNS. Its effects on the CNS are mediated by th e activation of neuronal heteromeric acetylcholine-gated ion channel r eceptors (nAChRs, also termed nicotinic acetylcholine receptors), In t he present study, we describe the neuroprotective effects of (-)-nicot ine in two animal models of parkinsonism: diethyldithiocarbamate-induc ed enhancement of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicit y in mice and methamphetamine-induced neurotoxicity in rats and mice. The neuroprotective effect of (-)-nicotine was very similar to that of the noncompetitive NMDA receptor antagonist (+)-MK-801, In parallel e xperiments, we found that (-)-nicotine induces the basic fibroblast gr owth factor-2 (FGF;2) and the brain-derived neurotrophic factor in rat striatum, The effect of(-)nicotine on the induction of FGF-2 was prev ented by the nAChR antagonist mecamylamine. We also found that (+)-MK- 801 was able to induce FGF-2 in the striatum. As trophic factors have been reported to be neuroprotective for dopaminergic cells, our data s uggest that the increase in neurotrophic factors is a possible mechani sm by which (-)-nicotine protects from experimental parkinsonisms.