Page 208 - Pagetit

6. CONCURRENT DISORDERS

(Richter & Weiss, 1999; Koob & Le Moal, 2001). Further, there is evidence
indicating blunted neurotransmission of neuropeptide Y (NPY) and
somatostatin in depression (Heilig & Widerlov, 1990; Rubinow, 1986), and
blunted neurotransmission of NPY in psychostimulant withdrawal
(Wahlestedt et al., 1991). Based on the hypothesis that NPY and somatostatin
systems act in opposition to the CRF system (Heilig et al., 1994), there is heuristic
value in further investigating the role of NPY and somatostatin in substance
dependence. One hypothesis is that NPY and somatostatin may be endogenous
“buffers” against the stressor-induced release of CRF. Given the role of CRF
and NPY in behavioural responses to stress (Heilig et al., 1994), it is conceivable
that neurotransmission of CRF, NPY and somatostatin is mostly related to the
anxiety or stress-like symptomatology seen in both a subgroup of people with
depression and in those in substance withdrawal. The same argument can also
be made about the GABA system that has also been implicated in depression
(Lloyd et al., 1989; Petty, 1995), and alcohol and benzodiazepine dependence
(Andrews & File, 1993; Roberts, Cole & Koob, 1996), considering that
benzodiazepines that enhance GABAergic neurotransmission are anxiolytics.
Administration of psychoactive substances, such as cocaine and alcohol,
modulate neurotransmission of CRF (Goeders, Bienvenu & de Souza, 1990;
Merlo Pich et al., 1995; Richter et al., 1995; Richter & Weiss, 1999) and NPY
(Wahlestedt et al., 1991), and thus could potentially restore temporarily the
hypothesized imbalance between the two systems.

Role of limbic structures in depression and substance dependence
Another common element between depression and substance dependence
is that most changes observed following antidepressant treatment or
administration of psychoactive substances are seen in limbic-related
structures, such as the frontal cortex, nucleus accumbens, olfactory
tubercle, hippocampus, amygdala, and the hypothalamus. For instance, in
the frontal cortex antidepressants alter the numbers of serotonin receptors
1A
(Peroutka & Snyder, 1980), and increase serotonin levels (Bel & Artigas,
1993). Antidepressants also produce supersensitive serotonin receptors
1A
in the amygdala (Wang & Aghajanian, 1980) and the hippocampus (de
Montigny & Aghajanian, 1978; Chaput, de Montigny & Blier, 1991). Chronic
antidepressant treatments also enhance dopaminergic activity in the
nucleus accumbens (Nomikos et al., 1991) and upregulate GABA receptors
A
in the frontal cortex (Lloyd, Thuret & Pilc, 1985). In addition, CRF receptors
are decreased in the frontal cortex of individuals with depression (Nemeroff
et al., 1988); electroconvulsive shock increases NPY brain levels in the frontal
cortex, the hypothalamus and the hippocampus (Wahlestedt et al., 1990);
and desmethylimipramine increases the numbers of somatostatin receptors
in the nucleus accumbens (Gheorvassaki et al., 1992).
Similarly, considerable evidence suggests an important role for limbic-
related structures in substance dependence and withdrawal. For example,

187

Chapter_6 187 19.1.2004, 11:48