tions—hence its use by those trying to relax or concentrate. Stress increases the smoker’s nicotine consumption. An increase in respiratory rate and heart rate has been observed with NRT. Sleeplessness has also been reported in patients using NRT (Gourlay et al., 1999). Nicotine overdose is remarkably difficult to achieve with NRT (Labelle and Boulay, 1999), however, it occasionally complicates the use of nicotine-containing insecticides. In these cases, central symptoms—initially tremors, nausea, vomiting, and possibly convulsions—give way to signs of central depression and neuromuscular blockade (Saxena and Scheman, 1985).

Memory and Cognition

Although there is considerable interest in the potential effects of nicotine on cognition (Emilien et al., 2000; Waters and Sutton, 2000), this has not been formally evaluated in individuals receiving NRT. Activation of nAchRs containing the α7 subunit results in Ach release and calcium activation, and both effects have been implicated in memory formation and cognition (Kem, 2000). Recent interest has been focused by co-immuno-precipitation of the amyloid A β(1–42)-fragment and the α7nAchR from the dendtritic plaques of Alzheimer’s disease (AD) lesions (Wang et al., 2000a). The β-fragment of amyloid A binds to the receptor and prevents its activation by nicotine, potentially implicating defective nAchR activation in the pathogenesis of AD. Again, although there is some evidence for a slowing of deterioration of AD in individuals who smoke (Debanne et al., 2000; Doll et al., 2000; Jarvik, 1991; Lopez-Arrieta et al., 2000; Merchant et al., 1999), along with a considerable literature relating to the use of cholinesterase inhibitors for this condition, NRT has not been formally evaluated in AD.

Addiction

The Biological Basis of Addiction. Although tobacco products contain several thousand chemicals, nicotine is considered to be the principal constituent in tobacco that leads to the persistent use of tobacco products (U.S. DHHS, 1988). However, other yet unknown constituents in tobacco may also have a role in the maintaining the use of tobacco. For example, smokers experience a reduction of monoamine oxidase (MAO) activity in the brain (Berlin et al., 1995) as a result of some constituent in smoke (Fowler et al., 1996); inhibition of MAO may result in antidepressant activity (Oxenkrug, 1999) and contribute to the high prevalence in smoking among individuals with depressive disorders. Physical addiction to nicotine is associated with euphoriant and other psychoactive effects, the development of tolerance, and the experience of withdrawal symptoms



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