Neurobiological substrates of nicotine addiction
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Almost 10 years ago the United States Surgeon General recognized tobacco-smoking as the number one cause of death in the USA that could be prevented, if individuals quit smoking (US Department of Health and Human Services 1988). In the same report, it was also indicated that nicotine is the main component of cigarettes that leads to the habit of smoking because the individual gradually becomes addicted to nicotine and, therefore, tobacco smoking is continued in order to continue the administration of nicotine. In that sense, nicotine is considered to be as addictive as other drugs of abuse such as opiates, amphetamines and ethanol. The fact that nicotine is addictive is indicated by the fact that smokers frequently fail to quit, with as high as 80% of individuals attempting to quit, resuming smoking within a year, even though these individuals are often fully aware of the potential harmful effects of smoking on health. One of the reasons that quiting smoking is difficult is because when a heavy habitual smoker stops smoking then the person suffers from several withdrawal symptoms, such as depression, anxiety, irritability, restlesness and increased appetite. These symptoms make the person crave and desire tobacco smoking in order to alleviate the suffering resulting from these symptoms, and “cure” the nicotine withdrawal symptoms. In the brain, nicotine produces its effects by attaching to and “activating” specific sites called receptors, and more specifically, on a type of receptor called acetylcholine receptor. This receptor is called acetylcholine receptor because a substance that is naturally found in the brain, called acetylcholine, normally attaches to these receptors. There are actually several subtypes of acetylcholine receptors. The purpose of the present studies is to investigate to which subtypes of acetylcholine receptors nicotine attaches in order to produce the pleasurable effects that habitual tobacco smokers experience. Other experiments will explore which of these acetylcholine receptor subtypes have changed their normal function during repeated nicotine administration, so that when nicotine is no longer available in the brain to attach to these receptors, these receptors’ actions lead to a series of events that produce the aversive symptoms experienced during nicotine withdrawal. Another series of experiments will investigate whether repeated failed attempts to quit smoking lead to an increased severity in the withdrawal symptoms, and thus, making it harder for people to quit smoking. The same experiments will also test whether the longer an individual has been a smoker the harder it is to quit smoking because for these individuals the pleasurable effects of nicotine are greater compared to the pleasurable effects of nicotine experienced by an individual that just started smoking. Further, other experiments will test whether the more times an individual has tried to quit smoking and failed, the harder it is to quit smoking, because again, for this individual nicotine has strong and powerful pleasurable effects. Finally, other studies will investigate which parts of the brain that contain acetylcholine and opioid receptors (the receptors on which opiate drugs and endorphins attach) are involved in the production of the nicotine withdrawal symptoms. All of the studies described above will be done in rats because such invasive studies that require injection of small amounts of nicotine and other drugs directly into the brain, or administration of drugs that have not been studied sufficiently to determine whether they have toxic effects in humans, cannot be done in humans; and such invasive experiments are the types of experiments that will enable us to study exactly which parts of the brain and receptor subtypes are responsible for the development of nicotine addiction and for the aversive symptoms of nicotine withdrawal. These studies will hopefully provide us with valuable information that will help us design effective treatment programs that involve both behavioral and pharmacological techniques, to help people to quit smoking, and thus, avoid the detrimental effects of tobacco smoking on health.