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