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.


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.


  • 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.


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.


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