Nicotine, addictive nature

The pleasure derived from using tobacco is linked to the stimulation of dopamine-dependent neurotransmitter pathways in the brain, particularly in the meso-limbic system. The precise nature of this link remains controversial, but many of the neurophysiological processes underlying nicotine addiction are common to other addictive drugs with diverse pharmacological actions such as opiates, cannabis, alcohol and cocaine. 

Laviolette, S. R. and van der Kooy, D. The neurobiology of nicotine addiction bridging the gap from molecular to behavior. Nature Rev. Neurosci. 5 55-65,2004. 

In studies with experimental animals, the reinforcing properties of nicotine seem to be relatively weak and do not appear to be sufficiently powerful to explain the highly addictive nature of tobacco smoke (Donny et al. 2003 Balfour 2004). An early study by Goldberg and colleagues (1981) using squirrel monkeys showed that... 

Evidence from the tobacco industry documents, from research studies that measure free-base directly in tobacco smoke particulate, and from examination of smokeless tobacco products, all show that the level of free-base nicotine as delivered to the tobacco user is a critical variable in the acceptance of tobacco products and their continued use. The physiological impact of the rapid delivery of nicotine in the free-base form is a critical determinant of continued nicotine-seeking behavior, with the unintended consequences of exposure to the other toxic components of tobacco smoke and smokeless tobacco. Evaluating total delivered nicotine alone is not sufficient to characterize product differences. To fully understand the influence nicotine has on the allure of these products, both total and free-nicotine levels must be measured. A comprehensive understanding of nicotine delivery is needed to help find effective means for breaking its addictive nature and, ultimately, in reducing the morbidity and mortality associated with tobacco use. The levels of free-base nicotine must be included as part of any effort to achieve a better understanding of how tobacco products themselves influence their continued use. 

Royal College of Physicians. (2000) Nicotine addiction in Britain a report of the tobacco advisory group of the Royal College of Physicians. Royal CoUege of Physicians of London, London Russell MAH (1971) Cigarette smoking natural history of a dependence disorder. Br J Psychol 44 1-16... 

Approximately 40-60 mg of nicotine (43) is a lethal dose for an adult human the LD50 i.v. in mouse is 0.3 mg/kg (Wink, 1993). This base is the main pharmacologically active component of tobacco smoke and probably is responsible for the addictive nature of cigarettes. The pharmacology of nicotine and other Nicotiana alkaloids has been reviewed (Fodor and Colasanti, 1985). Nicotine mimics acetylcholine and activates acetylcholine receptors (Wink, 1993). 

Pontieri FE, Tanda G, Orzi F, et al Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature 382 235-237, 1996 Pontieri FE, Zocchi A, Orzi F Mapping of functional changes associated with administration of substances of abuse in the rat. Funct Neurol 13 311-326, 1998 Preble E, Laury GV Plastic cement the ten cent hallucinogen. Int J Addict 2 271— 272, 1967... 

Pontieri FE et al. Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature 1996 382(6588) 255—257. 

The methods discussed above have been widely used to assess the effect of either continuous or intermittent nicotine on nAChR functions and brain biochemistry (Matta et al. 2007). For models of nicotine withdrawal, see the chapter by Malin in this volume. Given the intrinsic advantages and limitations of each approach, the non-contingent nature of most administration regimes and the absence of associated cues, it is important that these paradigms are not assumed to model tobacco addiction per se. Sometimes, the experiments are conducted in concert with behavioural measures (e.g. precipitation of withdrawal with somatic signs), which give more credibility to the assertion that a state of nicotine dependence has been achieved (Kenny and Markou 2005). 

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Pontieri, Francesco E., Gianluigi Tanda, Francesco Orzi, and Gaetano Di Chiara. 1997. "Effects of Nicotine on the Nucleus Accumbens and Similarity to Those of Addictive Drugs." Nature 382 255-57. 

Mild cases of alkaloid poisoning can produce psychological effects that resemble peacefulness, euphoria, or hallucinations. People seeking these effects often become addicted to alkaloids. Alkaloid addiction frequently ends in death. Current estimates are over 400,000 deaths from alkaloid addiction in the United States per year, including both natural alkaloids like nicotine and cocaine, and synthetic alkaloids like metham-phetamine. Most of these deaths result from addiction to nicotine in tobacco, a particularly difficult addiction to overcome. 

A natural product is a compound synthesized by a plant or an animal. Alkaloids are natural products that contain one or more nitrogen heteroatoms and are found in the leaves, bark, roots, or seeds of plants. Examples include caffeine (found in tea leaves, coffee beans, and cola nuts) and nicotine (found in tobacco leaves). Morphine is an alkaloid obtained from opium, the juice derived from a species of poppy. Morphine is 50 times stronger than aspirin as an analgesic, but it is addictive and suppresses respiration. Heroin is a synthetic compound that is made by acetylating morphine (Section 30.3). 

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