Title : Neurobiology of Nicotine Addiction

Nicotine’s addiction liability is demonstrated by the high prevalence of cigarette smoking and low quit success rates, despite well-documented health risks. Even though most smokers endorse a desire to quit, very few (< 5%) actually do so in a given year without treatment, and only about 20–25% will achieve abstinence with 6 months or more of effective treatment. Cigarette smoking or tobacco use disorder (TUD) is the main cause of preventable death in developed countries, with an estimated number of 450,000 premature deaths in the U.S. and 5-6 million worldwide every year. Although, ~ 20% of US adults are currently smokers, cigarette smoking is disproportionately common among individuals with low socioeconomic status, low educational levels, and psychiatric comorbidities, including those with another substance use disorder

Tobacco products have been used for >1,000 years, and the key active psychopharmacological ingredient “NICOTINE”, has been studied for almost 200 years. Nicotine, an alkaloid found in tobacco leaves, has been used by humans for its psychoactive properties for thousands of years. It received an extraordinary amount of research attention for its role in tobacco use and as a possible treatment for physical and mental health disorders like schizophrenia. Nicotine addiction is the leading cause of preventable death and disease worldwide. Being the primary pharmacologic component of tobacco with highly addictive nature, it is responsible for its widespread use and significant withdrawal effects, results in challenges to smoking cessation therapeutics. Nicotine, the psychoactive component of tobacco smoke, produces diverse effects through several brain regions and neurochemical pathways. It is only in the last several decades that the cellular and physiological mechanisms underlying nicotine’s complex effects on brain function (including its abuse / dependence liability) and its effects on cognitive function, have begun to be revealed.

Cigarette smoking is arguably the most important preventable disease in the developed world. Formerly regarded solely as a “lifestyle choice,” smoking is now recognized as a chronic, relapsing disorder. Over the last several decades, considerable advances have been made in the understanding of addictive disorders in general, and of nicotine addiction specifically. Like all addicting drugs, nicotine causes a complex set of psychological, biochemical, and cellular effects. These directly lead to the changes in mood and pleasure that smokers often find satisfying.

Nicotine addiction often begins in adolescence and is partially attributed to the fact that adolescent brain is most susceptible to the neuro-inflammatory effects of nicotine. E-cigarettes have emerged as the most common mode of nicotine delivery among youth across the U.S. Its use is most prevalent among adolescents’ and by vaping nicotine products, adolescents’ do not have an awareness and understanding of nicotine and its presence within E-cigarettes products. In adults, e-cigarettes are a potential cessation aid, while adolescents who have never before smoked, e-cigarette use is associated with initiation or escalation of cigarette smoking

Nicotine affects the nervous system through the action of nicotinic acetylcholine receptors (nAChRs) and involvement of the ventral tegmental area (VTA) has been extensively studied.  The contribution of dopamine (DA) and GABA (γ-aminobutyric acid) neurons, and their afferences and efferences, are crucially involved in the addiction process. The shift from the acute effects of nicotine to the development of a dependence state might involve a switch in the balance between the role of DA and GABA neurons in the VTA. Acute action might signal the rewarding effect of nicotine, but long-lasting desensitization might represent a cellular correlate of tolerance

Most recently, neuroimaging techniques such as positron emission tomography (PET), single photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI) have made it possible to study the actions of nicotine and cigarette smoking on brain circuits and processes underlying addiction and cognition in the human brain in vivo.

However, the neurobiological mechanisms underlying nicotine’s impact on brain function and behavior still remain incompletely understood

Take home message

• Nicotine, an alkaloid found in tobacco leaves, has been used by humans for its psychoactive properties for thousands of years
• Nicotine affects the nervous system through the action of nicotinic acetylcholine receptors (nAChRs) — ionotropic receptors that are widely distributed through the brain.
• Nicotine activates nAChRs in DA neurons of the VTA, an activation that is followed by desensitization on continued exposure to nicotine
• Acetylcholine from brainstem nuclei might exert a profound modulatory effect on both populations of VTA neurons through the activation of nAChRs
• The shift from the acute effects of nicotine to the development of a dependence state might involve a switch in the balance between the role of DA and GABA neurons in the VTA

Dr. Meera Vasami is a Tenured Professor and Director of the WHO Collaborative National Drug Dependence Treatment Center at All India Institute of Medical Sciences. She holds a PhD from University of Delhi and completed postdoctoral training at AIIMS. Dr. Vasami received prestigious awards from the National Institute on Drug Abuse, chaired Addiction sessions at American Psychiatric Association meetings (2002–2012), and was awarded a UN Fellowship at the University of Glasgow. She is an elected Fellow of the Royal Society of Chemistry and Member of the National Academy of Medical Sciences. She has been invited to publish chapters on addiction for “Elsevier Publications”; in “International Series of Addiction” Praeger Publications, USA"; in "Advances in Psychology “Nova Science Publishers’, Inc. USA". in "Genomics and Health in the Developing World” Oxford Publishers" ; in "Substance Use Disorder, Indian Publishers"