Nicotine protects cultured striatal neurones against 4–methyl–D–aspartate receptor–mediated neurotoxicity

Abstract

The role of cholinergic mechanisms in JV–methyl–D– aspartate (NMDA)–mediated 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 degeneration as assessed by MTT staining, crystal violet incorporation and determination of microtuhule– associated protein 2. The NMDA–induced neurodegeneration was strongly inhibited by the co–application of two non–selective cholinergic agonists, acetylcholine or carba– chol. This protective effect appears to be mediated by nicotinic receptors since it was insensitive to the muscarinic antagonist atropine but mimicked by nicotine, nornico– tine and l, l–dimethyl–4–phenyl–piperazinium. Moreover, the nicotine–evoked neuroprotection was inhibited by the central nicotinic antagonist hexamethonium. Therefore, this study suggests that cholinergic interneurones play an important role in neuronal survival in the striatum. © Rapid Communications of Oxford Ltd.