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6. CONCURRENT DISORDERS

Satel et al., 1991), opioids (Haertzen & Hooks, 1969; Henningfield, Johnson
&Jasinski, 1987; Jaffe, 1990), ethanol (Jaffee, 1990; Edwards, 1990; Bokstrom
& Balldin, 1992; Goodwin, 1992; West & Gossop, 1994; Schuckit et al., 1997)
and nicotine (West et al., 1984; West & Gossop, 1994). This depressive
symptomatology is conceptualized to reflect alterations in reward and
motivational processes (Markou, Kosten & Koob, 1998). This similarity and
neurobiological evidence (reviewed below) suggest several commonalities
in the neurobiology of the symptomatology of depression and substance
dependence that support either of the first two hypotheses described at the
beginning of this chapter.
Alterations in the neurotransmission of serotonin, norepinephrine,
acetylcholine, dopamine, GABA, corticotropin-releasing factor (CRF),
neuropeptide Y(NPY) and somatostatin have been observed in individuals
with depression (Caldecott-Hazard et al., 1991; Markou, Kosten & Koob, 1998).
In animals most of these neurotransmitter systems are also modulated by
antidepressant treatment, suggesting their involvement in the mode of action
of antidepressant drugs. Many of these same systems have also been
implicated in withdrawal from psychoactive substances, though not all
systems have been implicated in withdrawal from every psychoactive
substance. Furthermore, some of these systems are implicated directly in the
affective/depressive aspects of substance withdrawal that constitute the
common symptomatology of substance dependence and depression
(Markou, Kosten & Koob, 1998).

Serotonin
Decreased serotonergic neurotransmission is one of the most consistent
changes occurring during withdrawal from a variety of substances, such as
stimulants (Parsons, Smith & Justice, 1991; Imperato et al., 1992; Rossetti,
Hmaidan & Gessa, 1992; Weiss et al., 1992; Parsons, Koob & Weiss, 1995),
ethanol (Rossetti, Hmaidan & Gessa, 1992; Weiss et al., 1996) and
benzodiazepines (Lima, Salazar & Trejo, 1993). Interestingly, in the case of
stimulant withdrawal, the decreases in serotonin levels in the nucleus
accumbens were larger and appeared earlier than the decreases in dopamine
(Parsons, Smith & Justice, 1995); and during ethanol withdrawal, the decreases
in serotonin levels were more resistant to reversal by further ethanol self-
administration than the decreases in dopamine (Weiss et al., 1996).
Serotonin appears to be critically involved in depression and it is
hypothesized that reduced serotonegic neurotransmission mediates
depression (Schildkraut, 1965; Coppen, 1967). Cerebrospinal fluid measures
reflecting central serotonin activity in humans with depression provided
evidence of reduced serotonergic activity (Caldecott-Hazard et al., 1991).
Accordingly, some of the most effective antidepressants are serotonin
selective reuptake inhibitors (SSRIs), with almost all SSRIs thus far tested
being effective in treating depression (Caldecott-Hazard & Schneider, 1992).

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