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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

during withdrawal from psychostimulants (Parsons, Smith & Justice, 1995;
Richter & Weiss, 1999) or ethanol (Rossetti, Hmaidan & Gessa, 1992; Merlo
Pich et al., 1995; Weiss et al., 1996) dopamine and serotonin levels are
decreased in the nucleus accumbens, while CRF levels are elevated in the
amygdala. Furthermore, blockade of opioid receptors in the nucleus
accumbens or the amygdala readily induces some affective signs of opioid
withdrawal (Koob, Wall & Bloom, 1989; Stinus, Le Moal & Koob, 1990), while
blockade of dopamine receptors in the nucleus accumbens produces at least
the somatic signs of opioid withdrawal (Harris & Aston-Jones, 1994). Limbic
structures, such as the VTA, nucleus accumbens, hippocampus and the frontal
cortex are also critically involved in nicotine dependence (Dani & Heinemann,
1996; Kenny & Markou, 2001). Taken together, these data suggest that
alterations in several neurotransmitter systems implicated in depression may
also mediate dependence on psychoactive substances, and these
commonalities may underlie the comorbidity between these psychiatric
disorders.

Discussion and conclusions

In summary, clinical, epidemiological and neurobiological evidence, together
with theoretical considerations, suggest several commonalities in the
neurobiology of substance dependence, and of schizophrenia and depression
that support the first three hypotheses discussed at the beginning of this
chapter. The most likely neurobiological substrate underlying mental illnesses
and substance dependence in general is dysfunction in the mesolimbic
dopamine system. However, the many neurochemical effects of psychoactive
substances, and the many behavioural expressions of mental illnesses suggest
that there may be a number of causative factors. Research into the
comorbidity of substance dependence and mental illness will illuminate
common causative, preventative, and treatment factors. Few epidemiological
studies directly address this issue and international research is lacking.
Breslau and colleagues determined that in terms of depression and tobacco
smoking, it appears that both processes are operating, i.e. depression
predisposes to tobacco smoking and tobacco smoking predisposes to
depression (Breslau, Kilbey & Andreski, 1993; Breslau, 1995; Breslau et al.,
1998). In terms of other psychiatric disorders and substance dependence in
general, a retrospective study concluded that antisocial personality disorder
(see Box 6.1) and phobias generally appeared before the onset of substance
dependence, while for all other psychiatric disorders, the disorder appeared
before the onset of substance dependence for almost half of the cases, and
for the remaining half the reverse was true. Finally, a study on schizophrenia
and substance dependence concluded that a unidirectional causality for the
two disorders was not supported by the data (Hambrecht & Hafner, 1996).
These investigators found that 30% of patients with both schizophrenia and
substance dependence use alcohol or illicit drugs before the first signs of

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