As
suggested by its name, the focus of Smoking and Nicotine Dependence Research
is on the mechanisms and processes that contribute to the development
and maintenance of tobacco use. This endeavour is carried out at several
levels of analysis.
Drug Self-Administration Model
A
critical component of the investigations relies on animal models of nicotine
dependence, called drug self-administration, in which animals do work,
such as pressing a lever, to obtain intravenous infusions of nicotine.
Studies of this kind, which were pioneered by the research staff of this
section, constitute a model of voluntary nicotine delivery that mimics
the delivery of nicotine to cigarette smokers; the value of this model
is attested to by the fact that it has been adopted by a number of research
laboratories internationally. In our research, this model allows us to
discover the cellular and neurochemical elements that play a key role
in nicotine addiction.
Funded
by the US National Institute on Drug Abuse, we have used the model to
build on the well-known fact that a part of the motivational valence of
drugs of abuse is due to their action on dopamine systems in the midbrain.
Our research has shown that nicotine activates in addition a particular
set of brainstem neurons that use a different neurochemical, acetylcholine,
for cellular communication. This is exciting neuroscience research because
it represents the discovery of novel circuitry that contributes to drug
dependence. However, the research also has longer-term practical implications,
because the identification of such mechanisms opens the door to understanding
the biological diversity in risk factors, as well as to identifying targets
for medication development.
Antibodies against Nicotine
We
are also involved in research with a more immediate application to medication
develop-ment in which we have used our animal model to investigate the
utility of antibodies against nicotine as a potential therapeutic tool.
This pre-clinical research has been done in partner-ship with Immulogic
Pharmaceuticals of Waltham Massachusetts (now a part of Cantab Pharmaceuticals
of the UK).
Interactions of Alcohol and Nicotine
Another
effective partnership for us has been with the Alcohol Research Group
at the University of Indiana. Thanks to an international collaborative
award from the US National Institute on Alcohol Abuse and Alcoholism,
shared with Dr. A.D. Lê of the Centre and
Dr. T.K. Li of Indiana, we have been working to determine the differences
and commonalities in the interactions of alcohol and nicotine in reinforced
behaviour across animal strains bred selectively for ethanol consumption.
This is an important area of investigation because it addresses the question
of a genetic link to the epidemiological observation that excessive use
of alcohol and tobacco co-occur.
Nicotine Dependence in Adolescent Smokers
This
has been a year of new directions for our research team since it has seen
us begin a study of nicotine dependence in adolescent smokers. With the
generous support of a grant from the Robert Wood Johnson Foundation, we
are examining trends in dependence in adolescent smokers between the ages
of 12 and 18 years. This is the very first study globally in which actual
smoking behaviour is examined to determine both the biological and subjective
elements of smoking at an age at which experimentation with smoking is
high.
For
the upcoming year we will continue to maintain our integrative research
strategy, with the goal of characterizing dependence in ways that will
contribute to knowledge, treatment and prevention.
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