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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

sequence of DNA (marker) in each strain can be correlated with a quantitative
measure of a phenotype (e.g. amount of psychoactive substance self-
administered). Strong correlation of a phenotype with the presence of a
genetic marker suggests that the genetic sequence in the proximity of this
marker is involved in the regulation of this measure. Since the location of
the marker sequence is mapped on mouse chromosomes, such analysis
allows researchers to create genetic maps of loci important for the traits (Gora-
Maslak et al., 1991; Grisel, 2000).

Genetics of tobacco dependence

Heritability of tobacco dependence
There is evidence of significant heritability of tobacco use among different
populations, sexes and ages, as reported in a number of large-scale twin studies.
Family and twin studies have demonstrated a genetic effect on “ever” smoking
(or lifetime smoking, i.e. having smoked a cigarette at least once) (Cheng, Swan
& Carmelli, 2000; McGue, Elkins & Iacono, 2000). A major genetic influence on
the probability that an individual will become a smoker (“initiation”) of about
60% has been observed, and continuation of the smoking habit once smoking
has started (“persistence”) of about 70% (Kaprio et al., 1982; Carmelli et al.,
1992; Heath et al., 1995; Heath et al., 1999a; Koopmans et al., 1999; Sullivan
&Kendler, 1999; Kendler, Thornton & Pedersen, 2000).
The initiation of smoking is separate from the development of nicotine
dependence. One set of genetic factors was found to play a significant etiological
role in both initiation and dependence, while another set of familial factors,
probably in part genetic, solely influenced dependence (Kendler et al., 1999).
In other words, genetic factors that contribute to variation in smoking initiation
and dependence only partly overlap (Heath & Martin, 1993; Kendler et al., 1999;
Madden et al., 1999; Sullivan & Kendler, 1999; Heath et al., 2002).
Other aspects of smoking, such as the age when the onset of smoking
occurs, are also influenced by genetic effects in both sexes (Heath et al., 1999a;
Koopmans et al., 1999). Once smoking is initiated, genetic factors determine
to a large extent (86%) the quantity that is smoked (Kaprio et al., 1982;
Koopmans et al., 1999). In addition some aspects of smoking, such as “never”
smoking or intensity of smoking, showed a genetic contribution in males,
which was not clear in females (Edwards et al., 1995). A study in adolescents
demonstrated heritability estimates of over 80% for susceptibility to lifetime
smoking and current use (Maes et al., 1999). Other aspects of smoking are
also influenced by genetics, such as weight gain following cessation (Swan &
Carmelli, 1995).
It is evident that there are different genetic contributions to different
aspects of smoking behaviour, such as initiation, amount used, development
of compulsive use, withdrawal symptoms, and development of tolerance.
These factors individually contribute to the ICD-10 criteria for dependence

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