Grant: Project Grant

The societal costs of tobacco smoking are immense, with around 37,000 deaths each year due to smoking in Canada alone. Current quitting aids are of little help. Although nicotine clearly plays an important role in tobacco addiction, we have no clear idea what that role is. Oddly, when nicotine is tested in pure form, divorced from tobacco, it turns out to be a remarkably weak reinforcer (please note: in this context, a reinforcer is basically a reward). For example, neither human subjects nor animals will typically work hard to obtain injections of the drug. In this respect, nicotine is not in the same league as cocaine, amphetamine or heroin. There are, however, several less conventional ways by which nicotine could make tobacco addictive. For a start, nicotine has the ability to make other rewarding stimuli more powerfully rewarding (the so-called reinforcer-enhancing effect), which could, for example, allow nicotine to boost the effects of other addictive chemicals lurking in tobacco smoke. The proposed research will use animal models in order to better understand the addictive actions of nicotine. Unfortunately, much animal research has been done using excessively high doses of nicotine that do not translate readily to tobacco smoking; I propose to rectify this. We will investigate how nicotine exerts its reinforcer-enhancing effect (for example: is this an action of nicotine directly in the brain, and if so which types of nicotine receptor targets are involved?). We will also study whether nicotine's rewarding effects can "rub off" onto sensory cues through frequent association. We are also interested in finding ways to alleviate the unpleasant effects of nicotine withdrawal, which are often a barrier to quitting smoking. Overall, this research will deepen our understanding of the behavioural and chemical basis for tobacco addiction, which in turn should uncover new approaches to possible treatment.