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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

studies are used to identify regions of DNA that may be involved in the
expression of a trait such as substance dependence. Linkage studies examine
inheritance within related individuals, whereas association studies examine
inheritance in unrelated individuals. The concept of linkage is based on the
fact that genes located close to one another on a chromosome are more likely
to be inherited together from one parent, than are two genes located further
apart, due to the reassortment of genes that occurs during the process of
recombination. The genes are said to be “linked” since there is a greater
probability of the genes being inherited together. Linkage studies have been
an important tool for the localization of chromosomal regions contributing
to substance dependence; they support candidate gene studies and provide
potential identities of unknown phenotype-related genes (Arinami, Ishiguro
& Onaivi, 2000). The studies examine chromosomal locations that are
inherited together in people who have the phenotype in question (e.g. who
have nicotine dependence) in order to find areas of the chromosome
important for the condition.

Candidate gene approach
The candidate gene approach requires the selection of genes that may have
relevance to the phenotype in question. For example, it would be appropriate
to investigate nicotinic receptor genes when examining the genetics of
nicotine dependence. These studies examine candidate genes in people with
or without dependence, to look for differences between these groups.

Animal studies
Many genetic studies on substance dependence employ animal models.
Animal models have a great advantage in that the history of exposure to
psychoactive substances and most other environmental factors can be
controlled and manipulated allowing the use of powerful statistical analysis.
In addition, genetic studies in animals allow for specific breeding studies that
cannot be done with humans, and the results of these studies can be obtained
in a relatively short period of time. Moreover, while early studies could only
control the genetic make-up of experimental animals by in-breeding, modern
transgenic and knockout methodology allows the genotype of these animals
to be manipulated in a specified manner so that the role of specific genes in
the behaviours of interest can be investigated.
Transgenic animals (usually mice) are created by injecting a foreign gene
(transgene) into fertilized mouse eggs. The transgene integrates into the
mouse chromosome in one or several copies in a random location. The eggs
are then implanted into foster mothers. When the embryos develop to term,
a proportion of them will have the transgene integrated into the mouse
genome. The resulting transgenic founder animals are then bred to create
transgenic lines of mice (Picciotto & Wickman, 1998; Bowers, 2000). The

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