Today we're going to talk about nicotine. Nicotine is the addicting substance in tobacco. It's responsible for the repeated use of tobacco products even though they're very harmful. Tobacco's legal for, for adults. And the problem is that tobacco smoke is an enemy of public health. Let's talk about the good, the bad, and the ugly of nicotine. First, the good. Nicotine is a cognitive enhancer. It improves attention, memory, and computational abilities. It also improves motor abilities. The bad. Is that nicotine produces dependence. It maintains chronic smoking, and the use of other tobacco products. The ugly is that smoking causes 5 million premature deaths word, world wide per year. It reduces the lifespan of smokers by an average of ten years. And smoking is associated with various diseases such as chronic obstructive pulmonary disease, lung cancer, cardiovascular disease, and others. Can a smoker stop smoking? Well yes, but it may not be easy. Surveys reveal that 75% of smokers say they want to stop, and about 33% try to stop every year, but less than 3% actually stop. So, relapse is widespread, and nicotine addiction is powerful. Let's talk about the fundamental mechanism and action of nicotine. How does it work? We spoke about the nicotine receptor as an example when we were talking about drug receptors. The nicotine receptor is normally a receptor for acetylcholine. A well known neruo transmitter. The image shows both the side view and a top down view of the receptor. The side view's been shown before and nicotine acts like acetylcholine in that it binds to the receptor and opens the receptor channel. And ions flow through it. It's an ion channel receptor. Now if we examine the top down view of the receptor, we can get more information about them. First of all, nicotine receptors are composed of bundles of proteins, or protein subunits as they're called. And the brain makes several different kinds of sub unit proteins. So that the protein composition of nicotinic receptors can vary in different parts of the brain. The most common form of the receptor has alpha 4 and beta 2 protein sub units. It's called the alpha 4 and beta 2 subtype. And their other subtypes of receptors with kinds of protein supplements. When someone takes a puff of smoke from a cigarette the trans, the transfer of nicotine from the air in the lungs to the blood is very efficient. And because nicotine gets into the blood, it enters the brain very quickly. That is when within seconds after a puff. As it diffuses into the brain, it binds to the receptors and opens the ion channels and causes an influx of sodium ions. An efflux of potassium ions and sometimes an influx of calcium. As we've talked about earlier the brain doesn't have a way to remove or break down nicotine. It can break down acetylcholine very easily but not nicotine. So the effects of nicotine linger over time in the brain. Another point that needs to be made is that nicotine receptors can be located pre-synaptically. Up to this point, we've only talked about post-synaptic receptors, that receive neurotransmitters from the presynaptic nerve terminal. But there are also receptors on nerve terminals. And these are called presynaptic. A typical action for a presynaptic receptor is to alter neurotransmitter release into the synapse. It turns out that dopamine containing nerve terminals have presynaptic nicotine receptors. And when nicotine is taken, dopamine rel, dopamine release is increased in the nucleus accumbens and prefrontal cortex, which are reward areas. We think that the Alpha4-beta2 subtype may be responsible for this effect. It's also important to note that, through it's action at receptors, nicotine causes many effects. Other neurotransmitters are affected as well. And these include serotonin, glutamate and opioid peptides, for example. The effects of nicotine are varied, we've already mentioned that nicotine can enhance attention, mood and reaction time. It can also produce relaxation during stress. And it can cause an activation where blood pressure is increased and heart rate and cardiac output are increased as well. Many people who smoke have additional mental health problems. We refer to this as comorbidity, as I mentioned earlier. It's been found that patients with schizophrenia, depression and ADHD have a higher level of cigarette smoking than average. [COUGH] Now, for the demon in the brain, if you stop smoking, you can go through a very troubling and disruptive withdrawal syndrome. It's characterized by irritability, frustration, anger, anxiety, dysphoria and depression, a lack of concentration and so forth. Because the withdrawal syndrome is such a problem for smokers, relapse is high as we mentioned earlier. Is there treatment for smokers? Of course there is. There are many programs that include behavioral treatments and effective medications. Hopefully the treatments for smokers are becoming more effective and useful all the time. An important new device that has appeared is the electronic cigarette. The electronic cigarette, can, look like a cigarette, but it has no smoke. A heating element vaporizes a nicotine solution, so that you get to inhale nicotine without smoke. Obviously, this eliminates smoke toxicity. Because this device administers nicotine and thereby controls craving without smoke, like the nicotine patch, it's use in treatment is being considered. We don't have a lot of experience with electronic cigarettes, but we'll learn about them over the years. And we'll find out what the risks may be. An obvious risk is that nicotine is still add, addicting.