Presynaptic Actions of Nicotine in the CNS

Abstract

Nicotine stimulates the release of neurotransmitters in the CNS. One locus of its action is directly on the nerve terminal, through presynaptic nicotinic acetylcholine receptors. The nicotinic stimulation of dopamine release from striatal nerve terminals has been particularly widely studied. Nicotine acts in a dose-dependent manner (EC50=4µM) to elicit Ca2+-dependent dopamine release. The pharmacological profile of this action favours a ganglionic type of nicotinic receptor, but molecular biological techniques have revealed several subtypes of nicotinic receptors in the CNS. The pharmacological specificity of nicotine-evoked transmitter release is consistent with the receptor class identified by high affinity [3H]nicotine binding. This correlation is supported by the loss of such binding sites following nerve degeneration after lesion experiments or in degenerative diseases, and subcellular fractionation expermients indicate that a high proportion of [3H]nicotine binding sites are associated with isolated nerve terminals. Thus presynaptic nicotinic receptors may constitute a major target of nicotine in the brain.KeywordsDopamine ReleaseNicotinic ReceptorNicotinic Acetylcholine ReceptorPresynaptic ActionPresynaptic ReceptorThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.