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Harm reduction in nicotine addiction: helping people who by Tobacco Advisory Group of the Royal College of Physicians

By Tobacco Advisory Group of the Royal College of Physicians

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In the desensitised state, receptors are temporarily unreactive and their ion channels are closed. It used to be thought that nicotinic receptors only assume a desensitised state when exposed to high, near-lethal concentrations of nicotine. However, this conclusion was drawn from work on peripheral nicotinic receptors. In the brain, nicotinic receptors are generally much more prone to desensitisation, and some can even be turned off by levels of nicotine experienced on a daily basis by smokers.

12,13 Therefore, these anatomical considerations suggest that nicotine could exert a widespread influence on the brain through actions on nicotinic cholinergic receptors. Nicotinic receptors are located on the outer surface of neurons and help to regulate their electrical activity. They do this principally by controlling the entry of electrically charged chemicals (ions, particularly sodium and calcium) into cells. 3). In the absence of an agonist, the nicotinic receptor assumes a ‘resting’ shape in which N Me N Nicotine tobacco Acetylcholine (ACh) natural neurotransmitter Neuronal nicotinic acetylcholine receptor nAChR (CH3)3NCH2CH2OCCH3 O RESPONSE Tobacco addiction Natural physiological functions?

Nature 1996;383:713–6. Mansvelder HD, Keath JR, McGehee DS. Synaptic mechanisms underlie nicotine-induced excitability of brain reward areas. Neuron 2002;33:905–19. Gioanni Y, Rougeot C, Clarke PBS et al. Nicotinic receptors in the rat prefrontal cortex: increase in glutamate release and facilitation of mediodorsal thalamo-cortical transmission. Eur J Neurosci 1999;11:18–30. Guo JZ, Tredway TL, Chiappinelli VA. Glutamate and GABA release are enhanced by different subtypes of presynaptic nicotinic receptors in the lateral geniculate nucleus.

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