Nicotine, which is an agonist—a substance that can mimic another, mimics acetylcholine by binding to neuronal nicotinic acetylcholine receptors (nAChRs), which are ligand-gated ion channels constructed from various subunits (Benowitz, 2010). As nicotine binds to the receptor, it generally causes depolarization of the neuron, allowing calcium and sodium to rush through the channels, and will act directly on the presynaptic terminal to release certain neurotransmitters — the catecholamines (Benowitz, 2008; Bock et al, 2008; Rowell, 1987). Dopamine is one of the main neurotransmitters released, a process that is common in addictive drugs. It is responsible for the rewarding feeling that accompanies smoking, which makes it a central part of the addiction (Drugs and the brain 2022).
As nicotine intake increases, neuroadaptation to it will also develop. This results in an increase of nAChRs as a way of response to nicotine-mediated desensitization of receptors (Benowitz, 2008). As receptors increase in numbers and can return to responsive states, subsequently pushing the smoker to take in more nicotine, tolerance for nicotine builds quickly in the brain. Smokers constantly need to intake more nicotine to reach the same effect, which builds nicotine addiction. There are also physical effects on behavioral traits of smokers under nicotine. As nicotine enters the brain and dopamine is released, feelings of pleasure arise, which motivates the smoker to smoke again in order to achieve the same high. Nicotine can also reduce stress and anxiety, and improve concentration and performance on tasks, which makes it an addictive substance (Rowell, 1987). Additionally, the absence of nicotine in a system that it had previously occupied will cause a series of withdrawal symptoms, such as increased irritability, depression, and anxiety (A. Dani et al., 2011). Another aspect of the behavioral response is conditioned behavior, where the smoker will relate certain cues — whether it be emotions, activities, or environment — to the rewarding aspects of nicotine. These cues often will trigger a relapse and create a cycle (A. Dani et al., 2011; Benowitz, 2010). However, there are pharmacological aids that can help a smoker during smoking cessation. Nicotine-replacement medications are an especially useful one, as it is able to provide relief from withdrawal symptoms as well as provide, to some extent, positive reinforcements as tobacco and nicotine had originally provided. Additionally, some nicotine medications may desensitize certain nAChRs, allowing the intake of nicotine to be less satisfying than before (Benowitz, 2008). There are also other forms of agents that can help with smoking cessation, such as antidepressants, varenicline, and clonidine (Benowitz, 2008).
References
A. Dani, J., Jenson, D., & I. Broussard, J. (2011). Neurophysiology of nicotine addiction. Journal of Addiction Research & Therapy, 01(S1). https://doi.org/10.4172/2155-6105.s1-001
Benowitz, N. L. (2008). Neurobiology of nicotine addiction: Implications for smoking cessation treatment. The American Journal of Medicine, 121(4). https://doi.org/10.1016/j.amjmed.2008.01.015
Benowitz, N. L. (2010). Nicotine addiction. New England Journal of Medicine, 362(24), 2295–2303. https://doi.org/10.1056/nejmra0809890
Bock, G. R., & Marsh, J. (2008). The biology of nicotine dependence. John Wiley & Sons.
Rowell, P. P. (1987). Current concepts on the effects of nicotine on neurotransmitter release in the Central Nervous System. Tobacco Smoking and Nicotine, 191–208.
U.S. Department of Health and Human Services. (2022, March 22). Drugs and the brain.
National Institutes of Health. Retrieved July 11, 2022, from
