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Ending the Tobacco Problem: A Blueprint for the Nation
claim has been reviewed in-depth by the Institute of Medicine (IOM) in its 2001 report, Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction (IOM 2001), and by the U.S. Department of Health and Human Services in the 1988 Surgeon General’s report, The Health Consequences of Smoking: Nicotine Addiction (DHHS 1988). These reports highlight the research literature showing that nicotine, through a complex set of mechanisms and actions that affect the neurochemistry of the brain, establishes and maintains dependence on tobacco use. The evidence derives from animal and human studies, from molecular biology and neurochemistry to behavioral studies. The evidence, in fact, is overwhelming. One of the main implications of addiction is the loss of control of drug (nicotine) use. This means that when a person would like to stop or reduce the level of consumption of an addictive drug, like nicotine, it is difficult to do so.
Physical dependence on nicotine is associated with psychoactive as well as positive and negative reinforcing effects, the development of tolerance, and the experience of withdrawal symptoms. Dependence is associated with direct and indirect effects of nicotine on brain neurotransmitters, which are directly related to the behaviors associated with addiction and withdrawal. In addition, behavioral factors, including conditioning, play an important role along with the neurochemical effects. Finally, there are some physiological effects of cigarette smoke independent of the nicotine that might contribute to the overall pleasure and addictive properties of nicotine.
Nicotine from cigarette smoke is rapidly absorbed in the lungs, from which it is quickly passed into the brain. Nicotine exerts its actions by binding to nicotinic cholinergic receptors (nAChRs) in the brain (Dani and De Biasi 2001). Composed of five subunits, the main receptor mediating nicotine dependence is believed to be the α4β2 nicotinic cholinergic receptor. Mice lacking the β2 subunit gene do not self-administer nicotine, nor do they exhibit other behavioral effects associated with nicotine exposure. The α4 subunit is associated with nicotine sensitivity. Mutations of that subunit lead to increased sensitivity to nicotine-induced reward behaviors as well as to effects on tolerance and sensitization (Tapper et al. 2004).
Nicotine affects many neurotransmitter systems: dopamine, norepinephrine, acetylcholine, serotonin, γ-aminobutyric acid, glutamate, and endorphins. The major effect of nicotine is to stimulate release of these transmitters. The result of dopamine release is critical to the reinforcing effects of nicotine and occur in the mesolimbic area, the corpus striatum, and the frontal cortex. A pathway of particular importance to drug-induced reward involves the dopaminergic neurons in the ventral tegmental area of the midbrain and the release of dopamine in the shell of the nucleus accumbens. Dopamine release signals a pleasurable experience. For example, the threshold for intracranial self-stimulation in rats, a model for brain reward, is lowered acutely with nicotine exposure, indicating greater reward.