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3. BIOBEHAVIOURAL PROCESSES UNDERLYING DEPENDENCE

metabolism of alcohol and nicotine by the cytochrome P450 enzymes in the
liver can be increased in this way, thus larger doses are needed for the drug
to achieve the same effects as it had prior to enzyme induction. Tolerance
can also develop due to changes in receptor number or sensitivity. These
concepts will be further discussed in Chapter 4.
Although tolerance and sensitization to different aspects of a drug’s effects
can coexist (Hyman & Malenka, 2001), sensitization and tolerance are
essentially separate phenomena.
Sensitization occurs in connection with the rewarding effects of psycho-
active substances, and appears to be very important in the acquisition of
persistent substance use (Schenk & Partridge, 1997). Pre-exposure to a drug
can reduce the latency period for experimental animals to acquire self-
administration, and also can result in lower than expected doses of a drug
having reinforcing effects (Schenk & Partridge, 1997). This sensitization can
occur either through pre-exposure or from environmental factors such as
stress (Antelman et al., 1980; Cador et al., 1992; Deroche et al., 1992; Henry et
al., 1995; Badiani, Oates & Robinson, 2000). A key feature of sensitization is
that it is long-lasting (Robinson & Becker, 1986). Conversely, tolerance to the
behavioural effects of a drug appears to be more transient, and associated
with high frequency of drug use in a short period of time (Schenk & Partridge,
1997). Again, it is important to emphasize that tolerance and sensitization
can coexist in respect to different aspects of the drug’s effects (Hyman
&Malenka, 2001), and that tolerance can have both acute and chronic aspects.

Individual differences

There are individual differences in biology and environmental factors that
mediate the reinforcing effects of psychoactive substances. Individual
differences in response to first drug use can determine who will be more likely
to use the drug again (Davidson, Finch & Schenk, 1993). In animal models,
there are clear behavioural differences that can predict which animals are
more likely to develop sensitization and learn to self-administer drugs more
quickly (Piazza et al., 1990; Hooks et al. 1992; De Sousa, Bush & Vaccarino,
2000; Sutton, Karanian & Self, 2000). These behavioural factors are related to
increased mesolimbic dopamine in susceptible animals, both at baseline and
following food and drug rewards (Sills & Crawley, 1996; Sills, Onalaja
&Crawley, 1998). These findings have led to suggestions that there may be a
behavioural phenotype associated with mesolimbic dopamine function in
humans that can predict those who are more susceptible to developing
substance dependence (Zuckerman, 1984; Bardo, Donohew & Harrington,
1996; Dellu et al., 1996; Depue & Collins, 1999).
To summarize, dependence-producing substances share the ability to
produce persistent changes in brain regions that are involved in the process
of incentive- motivation and reward, and such changes make these regions
hypersensitive (sensitized). There is a wealth of evidence to support this claim.

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