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3. BIOBEHAVIOURAL PROCESSES UNDERLYING DEPENDENCE

1996; Schultz, Dayan & Montague, 1997). This is why, although different
classes of psychoactive substances have different primary pharmacological
mechanisms of action, dopamine is important to the development of
dependence for all classes because of its critical role in response-
reinforcement learning. Almost all psychoactive substances with reinforcing
properties activate mesolimbic dopamine, either directly or indirectly.
According to these models, dopamine is released in response to an
unexpected reward. This leads to a strengthening of the synaptic connections
in neural pathways that led to the behaviour that was associated with the
reward. Although psychoactive substances act through a wide variety of
primary pharmacological mechanisms, almost all eventually influence
mesolimbic dopamine function, which is why dopamine is such an important
neurochemical in the neuroscience of dependence. Dopamine is released in
response to all unexpected rewards, thus reinforcing the behaviours that led
to the occurrence of that reward.

Dependence-producing drugs as surrogates of conventional reinforcers

Drug and non-drug (e.g. stimuli associated with food, water, sex) reinforcers
share behavioural and neurochemical similarities. For example, drug and
non-drug reinforcers share the property of activating dopamine transmission
preferentially in a region of the nucleus accumbens known as the “shell”
(Pontieri, Tanda & Di Chiara, 1995; Robbins & Everitt, 1996; Bassareo & Di
Chiara, 1997; Tanda, Pontieri & Di Chiara, 1997; Bassareo & Di Chiara, 1999).
Therefore, dependence-producing drugs reproduce certain central
neurochemical effects of conventional reinforcers (Di Chiara et al., 1993),
thereby obtaining motivational significance in the brain.
Dependence-producing drugs, however, differ from conventional
reinforcers in that their stimulant effects on dopamine release in the nucleus
accumbens are significantly greater than natural reinforcers such as food.
Whereas food increased dopamine levels in the nucleus accumbens by 45%,
amphetamine and cocaine increased dopamine levels by 500% (Hernandez
and Hoebel, 1988). The mesolimbic dopamine system reinforces behaviours
and signals that are associated with stimuli that are critical to survival, such
as feeding and reproduction. Because psychoactive substances also activate
this circuit so powerfully and reliably, the drug-taking behaviour and stimuli
associated with it are registered in the brain as being critically important.
The repetitive, profound stimulation of dopamine transmission induced by
drugs in the nucleus accumbens abnormally strengthens stimulus–drug
associations (Pavlovian incentive learning). By this mechanism stimuli that
are associated with or predictive of drugs are attributed great motivational
value, thus becoming capable of facilitating behaviour that is instrumental
to the self-administration of the drug.
Relapse to substance use is known to be triggered by cues previously paired
with substance use, by stress, or by the presence of the drug itself (Stewart,

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