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3. BIOBEHAVIOURAL PROCESSES UNDERLYING DEPENDENCE

which dopamine exerts this function has been termed “incentive
sensitization”. Thus, the brain becomes more sensitive, or “sensitized” to the
motivational and rewarding effects of psychoactive substances.
It is hypothesized that this process of incentive sensitization produces
compulsive patterns of drug-seeking behaviour. Through associative learning,
the enhanced incentive value becomes focused specifically on drug-related
stimuli, leading to more and more compulsive patterns of drug-seeking and
drug-taking behaviour.

Psychomotor sensitization
Most laboratory studies showing that the repeated administration of
psychoactive substances can produce sensitization of the mesolimbic
dopamine system involve two measures: measures of levels of dopamine and
its metabolites in the nucleus accumbens, and measures of the psychomotor-
activating effects of drugs, such as their ability to enhance locomotor activity
in laboratory animals. Studies on the psychomotor-activating effects of drugs
are relevant to dependence because the mesolimbic dopamine system
controls both locomotion and behaviour, and locomotion is an easily
observable behavioural assay of nucleus accumbens function (Wise &
Bozarth, 1987).
There is now considerable evidence that the repeated intermittent
administration of psychomotor-stimulant substances results in a progressive
increase in their psychomotor- activating effects. Psychomotor sensitization
has been shown for amphetamine, cocaine, methylphenidate, fencamfamin,
morphine, phencyclidine, ecstasy, nicotine and ethanol (Robinson & Berridge,
1993).
Sensitization is remarkably persistent, and animals that have been
sensitized may remain hypersensitive to the psychomotor-activating effects
of drugs for months or years (Robinson & Becker, 1986; Paulson, Camp &
Robinson, 1991). It is important to note that sensitization can develop even
after a drug has been self-administered (Hooks et al., 1994; Phillips & DiCiano,
1996; Marinelli, Le Moal & Piazza, 1998), and therefore, that the experimental
models of sensitization are valid models of human substance use.

Sensitization and drug reward
Studies show that sensitization results from the psychomotor-activating
effects as well as the rewarding effects of psychoactive drugs (Schenk
&Partridge, 1997). Thus, upon repeated exposure to drugs over time, their
subjective rewarding effects are increased. (Note that this is in contrast to
the short-term tolerance that may occur within a single session of drug intake.
Sensitization develops over days to weeks to months). It is thought that the
shift from substance use to substance dependence may be closely related to
the phenomenon of sensitization (Deroche, Le Moal & Piazza, 1999).

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