This is a final project for Coursera's Understanding the Brain: The Neurobiology of Everyday Life The University of Chicago

1. BRAIN AND NICOTINE
ADDICTION
UNDERSTANDING THE BRAIN: THE NEUROBIOLOGY OF EVERYDAY LIFE
FINAL PROJECT, EUGENE SHMATKO

2. INTRODUCTION
During the week 2 of the course Neurol Communication and Embodied Emotions I was fascinated how
neurotransmitters orchestrate our daily central nervous system and the complexity of neurocommunication. Thanks
to Professor Mason and her wonderfully created short video presentations I better understood fundamental
processes in the nervous system. Her presenting style and examples made the course exciting to learn and review.
For my professional reasons, nicotine addiction is one of topics of I was particularly interested in researching.
Understanding the Brain course inspired me to look at the problem from physiological and neurobiological aspects.
Nicotine addiction is one of the serious problems causing over 8 million deaths globally (1).
Out of 1.1 billion smokers more than 50 million are youth smokers. (2)
15% of global deaths are attributed to smoking
(1)www.who.int
(2)https://www.vitalstrategies.org/

3. FACTS
1. Nicotine addiction is one of the serious problems causing over 8 million deaths
globally (1).
2. Out of 1.1 billion smokers more than 50 million are youth smokers. (2)
3. 15% of global deaths are attributed to smoking
(1)www.who.int
(2)https://www.vitalstrategies.org/

4. INTRODUCTION TO ACETYLCHOLINE C7H16NO2
Acetylcholine (Ach) is the major neurotransmitter of the
parasympathetic nervous system that contracts smooth muscles,
slows heart rate, dilates blood vessels etc. It is also the mediator
released by motor neurons to activate muscles.
In brain it functions as neurotransmitter and neuromodulator
where around 4%-5% of Ach neurons are responsible for
normalizing the work of the CNS such as attentions, arousal,
memory, motivation, sleep etc. Acetylcholine consists of two
compounds the acetic acid and choline, thus being cholinergic, it
has excitatory or inhibitory effects in our nervous system.
Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013

5. RECEPTORS
In the nervous system there are two main acetylcholine
synaptic receptors (AchRs) consist of two major subtypes:
the metabotropic muscarinic receptors and the ionotropic
nicotinic receptors. In my case I will focus on neuronal
nicotine acetylcholine receptors (nAchR) in the CNS only and
their role in nicotine addiction and withdrawal.
File:Acetylcholine Pathway.png From Wikipedia, the free encyclopedia
https://onlinelibrary.wiley.com/doi/full/10.1111/jphp.12919

6. GETTING ADDICTED
STAGE 1
For a first-time smoker the initial effects of nicotine (tobacco toxin C₁₀H₁₄N₂) occur in sympathetic and
parasympathetic ganglia and for most ‘beginners’ parasympathetic activation starts immediately with the first
cigarette leading to dizziness, gastrointestinal tract contractions, increasing of blood pressure, unstable heart
rate etc. Parasympathetic system reacts to the toxin trying to protect the organism.
With repeated intake of cigarette, only sympathetic activation is observed: the blood pressure rises, inhibits
gastrointestinal activity, decreases of muscle sympathetic nerve activity. The nicotine slightly excites the
nervous system and the smoker may feel freshness. At this stage nicotine hasn’t yet reached the CNS, therefore
a smoker is not addicted and can, at any time, quit smoking.
The stage may last years and I observed that some may smoke occasionally at the social events only without
being addicted.

7. STAGE 2
Once nicotine overpasses gamato- encephalic
barrier (GEB), it, being a full agonist of nicotinic
acetylcholine receptors binds with them,
stimulating presynaptic acetylcholine receptors
and enhancing acetylcholine release and
metabolism.
The nAch receptors are widely distributed in
different brain regions, and are located in medulla,
basal ganglia, prefrontal cortex, hippocampus,
nucleus accumbens, hypothalamus and some
others. As I have mentioned above, one of the
main functions of acetylcholine in the CNS is
normalizing its work, its emotional condition and
function, thus the increase of nicotine may initially
alter the CNS excitability.

8. acetylcholine synapse
The reason why it happens is that in normal state every
receptor synthesizes and releases from 100–300 synaptic
vesicles in the synaptic cleft (Kuffler & Yoshikami, 1975), and
the CNS maintains its innate intensity of signal transition.
Prolonged stimulating the receptors with agonists, nicotine in
my case, triggers their counter-reaction leading to decrease in
synthesizing the amount of acetylcholine by neurons and in
overall decrease of activity. The neurons will be depended on
extra agonist influx of nicotine rather on synthesizing their
own acetylcholine.

9. STAGE 3
At this stage the smoker has to increase the dose to compensate the amount of
acetylcholine. This stage of dependency is critical. Any attempt to quit smoking
will cause abstinent syndrome indicating that the acetylcholine synapses need
more nicotine. The withdrawal syndrome is characterized by irritation, anxiety,
apathy and increased eating disorder and often depression. It is believed that
the main pathways associated with nicotine and depression are cortex,
hippocampus, thalamus (Bertrand D. The possible contribution of neuronal
nicotinic acetylcholine receptors in depression. Dialogues Clin
Neurosci.2005;7(3):20716.doi:10.31887/DCNS.2005.7.3/dbertrand. PMID:
16156379; PMCID: PMC3181734.)
Normalization the activity of nAChRs may take weeks or in some cases months
and only pharmacological and psychological or counseling therapies can
substantially reduce the withdrawal symptoms.
Photo by Abed Rahim Khatib/Flash 90.

10. NICOTINE AND OTHER NEUROTRANSMITTERS
• Another danger of nicotine is that binds to nicotinic receptors altering
many other neurotransmitters such as dopamine, serotonin, gamma-
aminobutyric acid, and glutamate effecting such neurofunctions.
• Therefore, smokers may experience more rapid cognitive decline
(Sabia S, Elbaz A, Dugravot A, Head J, Shipley M, Hagger-Johnson G,
Kivimaki M, Singh-Manoux A. Impact of smoking on cognitive decline
in early old age: the Whitehall II cohort study. Arch Gen Psychiatry.
2012 Jun;69(6):627-35. doi: 10.1001/archgenpsychiatry.2011.2016.
PMID: 22309970; PMCID: PMC3675806.)
• Some researches argue that long term smokers
may experience volume loss in several areas of
brain due to nicotine negative effect on
structural integrity of subcortical brain regions.
(Durazzo TC, Meyerhoff DJ, Yoder KK, Murray DE.
Cigarette smoking is associated with amplified
age-related volume loss in subcortical brain
regions. Drug Alcohol Depend. 2017 Aug
1;177:228-236. doi:
10.1016/j.drugalcdep.2017.04.012. Epub 2017
Jun 7. PMID: 28622625; PMCID: PMC6602081.)

11. ADDICTION AND BRAIN
Hypothalamus
• Main functions: The hypothalamus helps
manage your body temperature, hunger and
thirst, mood, sex drive, blood pressure and
sleep.
• Nicotine effects: worsen appetite and sleep.

12. Nucleus accumbens
Main functions: the neural interface
between motivation and action, playing a
key role on feeding, sexual, reward, stress-
related, drug self-administration behaviors
Nicotine effects: increase nervousness,
feelings of stress

13. Hippocampus
Main functions: learning and memory
Nicotine effects: weakening of assimilation
and memorization of information

14. CONCLUSION
Tobacco smoking is one of the legal drugs around the world and it effects not only the nervous
system but also the respiratory system, the circulatory system, the reproductive system, the skin, and
the eyes. Tobacco addiction is neurobiological phenomenon researched by psychologists,
pharmacologists, physicians, narcologists etc. In this project I decided to focus only on the nervous
system and the mechanism of nicotine addiction after taking the course Understanding the Brain:
The Neurobiology of Everyday Life.

15. This course introduced me to the complexity of our nervous system. It was an
honour to watch the video materials, read and go the quizzes. I appreciate what
professor Peggy Mason has done. She succeeded in explaining in simple terms the
work of the most difficult and still under-research organ- the brain