NICOTINE PROTECTS CULTURED STRIATAL NEURONS AGAINST N-METHYL-D-ASPARTATE RECEPTOR-MEDIATED NEUROTOXICITY

THE role of cholinergic mechanisms in N-methyl-D-aspartate (NMDA)-medi ated neuronal death was investigated using mouse striatal neurones in primary culture. A 30 min exposure of striatal neurones to increasing concentrations of NMDA resulted 24 h later in dramatic neuronal degene ration as assessed by MTT staining, crystal violet incorporation and d etermination of microtubule-associated protein 2. The NMDA-induced neu rodegeneration was strongly inhibited by the co-application of two non -selective cholinergic agonists, acetylcholine or carbachol. This prot ective effect appears to be mediated by nicotinic receptors since it w as insensitive to the muscarinic antagonist atropine but mimicked by n icotine, nornicotine and 1,1-dimethyl-4-phenyl-piperazinium. Moreover, the nicotine-evoked neuroprotection was inhibited by the central nico tinic antagonist hexamethonium. Therefore, this study suggests that ch olinergic interneurones play an important role in neuronal survival in the striatum.