The Brain's First Whiff of Nicotine

Chris - A new study sheds more light on how the brain responds to its first ever whiff of nicotine. By looking at activity in the brain tissue of a rat as it's exposed to nicotine for the very first time, Professor Daniel McGehee, at the University of Chicago, has found that the drug triggers changes in the brain's circuitry, which makes people much more likely to then get hooked.

Daniel - The dopamine system is this reward pathway. The effect of addictive drugs on behaviour is dependent on a change in dopamine signalling, so that's been a focus for our work and many other groups. We know that dopamine activates a specific type of receptor, a protein that's on the surface of many different neurones. And these receptors are excitatory - they depolarize the cell, causing it to fire more so more electrical activity occurs - and we know that that's the first step in the process. What our most recent study has shown is that this actually initiates a whole cascade of events. One of the things that happens is that the inputs that normally excite these dopamine cells become stronger. The synaptic connections - the points of connections between cells - are stronger after nicotine exposure.

Chris - So are you saying that the nicotine comes in, it stimulates some dopamine-producing nerve cells to make more dopamine, which the brain experiences as being a pleasurable experience, and at the same time, the cells that make that dopamine, which are connected to other nerve cells, begin in future to respond more strongly to those connections than they would have done before?

Daniel - That's a nice description of what our data and others have shown, yes. The connections are stronger and this is something that persists for days. What we're looking at is the steps that lead to that change. Even after the nicotine is gone, these connections remain strong for between five and ten days after exposure, and just to emphasise, that's a change in an animal that has not seen the drug before and it's in response to one exposure.

Chris - And when the person has had that change happen in their brain, what then makes the person keep reaching for the cigarette packet? Because if their cells are now producing more dopamine because the connections to them are stronger - the cells are getting more excitable than they were before - then why carry on smoking?

Daniel - Yes, that's a great question, and one that we would love to have a complete answer to. The transition from occasional use or a single exposure to the full-blown addicted smoker is a long and complex process that we really don't understand. We know that there are huge adaptations happening in the brain areas that we're looking at, but it's also very likely that other brain areas play critical roles. In adolescents who are experimenting with smoking, they will quite often sample cigarettes at a very low rate, like once a month, once every two weeks etc. One theory that I like is the idea that the duration that this increase in excitation in the pathway persists for is contributing to that process and establishes a framework for associating the tobacco and nicotine with pleasure, and that basically sets the stage for the progression to full-blown addiction. The progression is going to be involving this process but also almost certainly other processes that we don't yet understand.

Chris - Does it transfer to other drugs? Because if you rewire this circuitry which makes your brain much more prone to getting hooked on things, and then another drug comes along, does the tobacco pre-priming mean that some cocaine is much easier to get hooked on that it would be without this happening?

Daniel - That's certainly a possibility. It's beyond the scope of what we're looking at right now, but co-use of a variety of different substances is quite common, so the idea that exposure to one drug modifies or enhances the rewarding effects of another drug makes perfect sense to me, as far as I understand the system, and this could be one of the ways in which that could happen.

Chris - I think 75% of smokers say they would like to quit - that's the intended quit rate - though the successful quit rate is another matter. What about using this information to help people to quit or to not get hooked in the first place?

Daniel - I do think that this adds to the public health message that I think is being broadcast quite effectively in many parts of the world - that exposure to tobacco products and nicotine is potentially addictive and long-term exposure has hugely negative health consequences, and there's just no argument here. Even occasional and casual use of tobacco products could be inducing persistent effects on parts of the brain that we know are involved with reward and addiction. As far as the potential for treatment of the full-blown smoker who is trying to quit, we certainly hope that identifying steps in the process, in terms of cellular events and molecular events that are happening inside neurones, may lead to the identification of new drugs that will improve the abysmal quit rate that's out there. I do think that the most important message is that there are changes happening with the very earliest exposures, and they are part of the progression to full addiction.

Chris - Well they say that it only takes one cigarette to get you hooked, and that evidence does look compelling. That was Professor Daniel McGehee, from the University of Chicago - he's published that work in the Journal of Neuroscience this week.