Nicotine addiction

The majority of tobacco users continue their use because they are addicted to nicotine. By smoking, long term users modify their brain chemistry meaning it can be very difficult for individuals to stop.

The majority of tobacco users continue their use because they are addicted to nicotine. By smoking, long term users modify their brain chemistry meaning it can be very difficult for individuals to stop.

NICOTINIC ACETYLCHOLINE RECEPTORS (nAChRs)

Nicotine distilled from smoking a cigarette travels from the mouth, to the lungs and finally to the brain, where it binds to nicotinic cholinergic receptors. This binding results in the uptake of sodium and calcium, resulting in neurotransmitter release.

nAChRs are made up of five subunits, arranged symmetrically around the ion channel. The release of various neurotransmitters following nicotinic binding to the nAChRs plays a large part in the cycle of addiction associated with smoking.

NEUROTRANSMITTERS

  • Dopamine: This neurotransmitter is linked with pleasurable experience and reward. The release of dopamine in the nucleus accumbens is central to the addictive properties of smoking. Dopaminergic receptors in this part of the brain are central to drug induced reward.
  • Glutamate: This is the major excitatory neurotransmitter within the mammalian brain, central to both memory and learning. Nicotine results in glutamate increasing dopamine release.
  • GammaAminobutyric acid(GABA): This is the chief inhibitory neurotransmitter within the mammalian brain. Simply, it does the opposite of glutamate. By smoking, nicotine causes (initially an increased amount, but over the course of one hour) a reduced amount of GABA availability. This means dopamine released remains increased, and not inhibited by GABA.
  • Hypocretin 1 & 2: This neurotransmitter regulates wakefulness and appetite. Smoking causes attenuation of Hypocretin, increasing availability but also reducing the binding affinity of their receptors. This promotes smoking behaviour; as there is reduced hypocretin uptake users can become tired and irritable if they do not replenish hypocretin levels.

Also of note is that products in cigarette smoke, such as acetaldehyde, can also increase the addictive nature of smoking. Condensation products of acetaldehyde reduce activity of monamine oxidases, responsible for the metabolism of neurotransmitters such as dopamine. Inhibition on monamine oxidases therefore contributes to addictiveness by preventing metabolism of extra-neuronal dopamine.

Ultimately, prolonged smoking results in neuroadaptation. Withdrawal following prolonged exposure to nicotine results in an increase in the ‘brain-reward threshold.’ This demonstrates a central neuroadaption, and can explain the reduced perceived positive perception towards pleasurable stimuli when a smoker first quits.

Managing withdrawal is therefore paramount; fear of withdrawal can be enough to deter smokers from even attempting to quit.

CONDITIONED STIMULI (PSYCHOLOGICAL ADDICTION)

When compared to other drugs of abuse in experimental rats, nicotine’s properties of reinforcement are considerably weaker when compared to other addictive substances. It is therefore hypothesised that habitual behaviours can only be developed in ‘higher’ animals, where more complex cognitive skills can be developed.

Indeed, it has been showed that smoking nicotine free cigarettes is almost as satisfying as their nicotine containing counterparts, simply due to the habitual enjoyment, something that is not present in experimental rats. Repetition of smoking activity, for example with a certain friend or with an alcoholic drink, becomes a powerful cue for individuals to smoke.

 

Bibliography & Further Reading
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Blood AJ, Zatorre RJ. Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion. Proceedings of the National Academy of Sciences. 2001 Sep 25;98(20):11818-23.
Brandon TH. Negative affect as motivation to smoke. Current Directions in Psychological Science. 1994 Apr 1;3(2):33-7.
Carpenter CM, Wayne GF, Connolly GN. The role of sensory perception in the development and targeting of tobacco products. Addiction. 2007;102:136–47.
Crocq MA. Alcohol, nicotine, caffeine, and mental disorders. Dialogues in clinical neuroscience. 2003 Jun;5:175-86.
Cuijpers P, Smit F, ten Have M, et al. Smoking is associated with first-ever incidence of mental disorders: a prospective population-based study. Addiction 2007; 102: 1303–1309
Dani JA, De Biasi M. Cellular mechanisms of nicotine addiction. Pharmacol Biochem Behav. 2001;70:439–46.
Di Chiara G. Nucleus accumbens medial shell and core dopamine: differential role in behavior and addiction. Behav Brain Res 2002; 137: 75–114
Dwyer JB, McQuown SC, Leslie FM. The dynamic effects of nicotine on the developing brain. Pharmacol Ther. 2009;122:125–39.
Epping-Jordan MP, Watkins SS, Koob GF, Markou A. Dramatic decreases in brain reward function during nicotine withdrawal. Nature 1998; 393: 76–79.
Fowler JS, Logan J, Wang GJ, Volkow ND. Monoamine oxidase and cigarette smoking. Neurotoxicology. 2003;24:75–82.
Hawkins BT, Abbruscato TJ, Egleton RD, Brown RC, Huber JD, Campos CR, Davis TP. Nicotine increases in vivo blood–brain barrier permeability and alters cerebral microvascular tight junction protein distribution. Brain research. 2004 Nov 19;1027(1):48-58.
Kane JK, Parker SL, Matta SG, Fu Y, Sharp BM, Li MD. Nicotine up-regulates expression of orexin and its receptors in rat brain. Endocrinology. 2000;141:3623–3629.
Khantzian EJ. The self-medication hypothesis of substance use disorders: A reconsideration and recent applications. Harv Rev Psychiatry 1997; 4: 231-244.
Lasser K, Boyd JW, Woolhandler S, Himmelstein DU, McCormick D, Bor DH. Smoking and mental illness: a population-based prevalence study. JAMA. 2000;284:2606–10
Le Foll B, Wertheim C, Goldberg SR. High reinforcing efficacy of nicotine in non-human primates. PLoS One 2007; 2: e230
Lessov-Schlaggar CN, Pergadia ML, Khroyan TV, Swan GE. Genetics of nicotine dependence and pharmacotherapy. Biochem Pharmacol. 2008;75:178–95.
Lynch BS, Bonnie RJ. Growing up tobacco free — preventing nicotine addiction in children and youths. Washington, DC: National Academy Press; 1994. The nature of nicotine addiction; pp. 28–68.
Mansvelder, H.D., and McGehee, D.S. Long-term potentiation of excitatory inputs to brain reward areas by nicotine. Neuron 27(2):349-357, 2000.
Mansvelder, H.D.; Keath, J.R.; and McGehee, D.S. Synaptic mechanisms underlie nicotine-induced excitability of brain reward areas. Neuron 33(6):905-919, 2002.
Ratschen E, Britton J, McNeill A. The smoking culture in psychiatry: time for change. The British Journal of Psychiatry 2011; 198: 6-7.
Rose JE, Behm FM, Westman EC, Johnson M. Dissociating nicotine and nonnicotine components of cigarette smoking. Pharmacol Biochem Behav 2000; 67: 71–81.
Saccone SF, Hinrichs AL, Saccone NL, et al. Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Hum Mol Genet. 2007;16:36–49
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