So we all know smoking is bad for us – we were told when we were kids, and even the packets have warning messages and gruesome pictures to try and help us kick the habit! So why do people still smoke?
As most of you will already know, it’s the nicotine in cigarettes that is the primary cause of smoking addiction. The nicotine is absorbed when cigarette smoke is inhaled and goes on to affect normal body functions, as well as mood and cognition – this is because it binds to receptors in the body called nicotinic acetylcholine receptors (nAChs). These are usually activated by the neurotransmitter acetylcholine, but they are also sensitive to nicotine, and it’s this sensitivity that underlies nicotine addiction. Nicotine can induce mild euphoria, can stimulate attention focus, decrease appetite and relieve anxiety.
When nicotine binds to nAChRs on neurons in the mesolimbic reward pathway of the brain, it leads to excitement of the cell and release of the neurotransmitter dopamine. Dopamine has roles in memory, information processing, and emotions such as love. The nicotine also binds to nAChRs on neurons that regulate the reward pathway-associated neurons, and therefore induces further effects on dopamine levels. Binding of nicotine on nAChRs to other neurons like glutamate- and GABA-secreting neurons has a role in developing nicotine dependence – so nicotine binds at a variety of sites that all work together to develop addiction!
The Role of Dopamine
Dopamine is thought to play a central role in nicotine addiction and dependence. Dopamine is heavily involved in feelings of pleasure and fulfilment through the mesolimbic reward pathway in the brain. Blocking the dopamine receptors (there are 5 different dopamine receptors: D1-5 receptors) actually decreases the reinforcement of nicotine addiction, and smoking-cessation aids are being development to target dopamine signalling to help people quit.
The Role of Glutamate
Like we said before, nicotine can affect glutamate-secreting neurons as well as dopamine-secreting ones. Binding to nAChRs on these neurons leads to the release of glutamate, which then goes on to excite the dopamine-secreting neurons, leading to further dopamine secretion. So here nicotine is increasing dopamine levels indirectly.
One Mechanism of Nicotine Withdrawal
For a long time, exact mechanisms of nicotine withdrawal weren’t understood at all. One mechanism now thought to underlie withdrawal involved the CRF system in the brain. CRF is corticotrophin-releasing factor, and the CRF system plays a central role in motivating the body to continue to smoke. Withdrawal of nicotine activates this system in the amgydala of the brain, which then goes on to act on CRF receptors and produce the feeling of anxiety associated with smoking cessation. This contributes to the ‘relapse’ of want-to-be ex-smokers, and reinforces their cravings for cigarettes. The feelings of pleasure and reward delivered after relapse into smoking (from the dopamine signalling we mentioned earlier) help cement their addiction!
Addiction is incredibly complicated, but we’ve tried to cover some basic principles of nicotine addiction here! There are lots of VERY comprehensive reviews of the exact molecular mechanisms and nAChR-mediated mechanisms of smoking addiction, so if we’ve tickled your interest with this article, do go ahead and find out more!
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George O, Ghozland S, Azar MR, Cottone P, Zorrilla EP, Parsons LH, O’Dell LE, Richardson HN, & Koob GF (2007). CRF-CRF1 system activation mediates withdrawal-induced increases in nicotine self-administration in nicotine-dependent rats. Proceedings of the National Academy of Sciences of the United States of America, 104 (43), 17198-203 PMID: 17921249