Chapter 6 Single cell studies of the actions of agonists and antagonists on nicotinic receptors of the central nervous system

Abstract

This chapter focuses on the study of the pharmacology of nicotinic receptors of single central nervous system (CNS) cells using electrophysiological means. Both in vivo and in vitro preparations are discussed. In situ studies using extracellular electrodes to monitor changes in discharge rate is used to map the cholinoceptive areas of the brain. The nicotinic agonists are capable of both exciting and inhibiting neurons in some brain areas. The excitation is a direct postsynaptic action of acetylcholine (ACh); the inhibition may be direct, but most likely results either from indirect inhibition through synaptic connections, or as a result of activation of a membrane conductance as the result of the preceding excitation. The in vitro brain slice preparation has allowed a more precise characterization of the receptor and currents underlying the nicotinic effects. In all areas of the CNS studied so far, central nicotinic receptors have been found to more closely resemble those of peripheral autonomic ganglia than those subserving nicotinic transmission at the neuromuscular junctions (n.m.j). Specifically, α-bungarotoxin, a neurotoxin which blocks nicotinic signal transmission between nerve and muscle, but not between peripheral nerves, also fails to block the effects of ACh and nicotine on central neurons. The ionic nature of the nicotinic effect resembles that of both peripheral nerve and muscle; ACh opens a membrane cation-selective channel which allows positive charge to enter the cell-producing depolarization.