Knockout mice as animal models for studying nicotinic acetylcholine receptor function

作者: L. M. Marubio , J.-P. Changeux

DOI: 10.1007/978-3-642-57079-7_20

关键词: NicotineAcetylcholineAcetylcholine receptorNicotinic acetylcholine receptorNicotinic agonistNeuroscienceReceptorGene knockoutAgonistBiology

摘要: Nicotinic acetylcholine receptors (nAChRs) are expressed in muscle, the central nervous system (CNS), and peripheral (PNS). Nicotine, a specific agonist of these receptors, exerts diverse cellular behavioural effects. Aside from its addictive properties, nicotine acts as cognitive enhancer, an anxiolytic, antinociceptive substance, seizure inducer. Pharmacological experiments with nicotinic agonists antagonists have pharmacologically helped to elucidate function (ACh) nAChRs CNS periphery. However, selective ligands for multiple isoforms neuronal still scarce. A recent approach involves genetic manipulations mice which result “knockouts” genomic null mutations. Specific genes encoding deleted, thus, essence, providing highly selective, albeit irreversible, “antagonist”. Although there some inherent problems using this (developmental requirements or compensatory effects, example), gives new insights into pharmacology functional role complex neurobiological systems. In chapter we will focus on knockout lacking nAChR subunit that allowed molecular dissection subtypes led identification particular subunits involved nicotine-elicited behaviours addition being used models several human pathologies.

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