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tressful life events are among the most potent
factors that trigger or induce depressive episodes in
humans. The brain responds to stress experiences in a
complex manner related to the activation and inhibition
of neurons that are involved in sensory, motor, auto-
nomic, cognitive, and emotional processes. Chronic
stress, which is known to be accompanied by hyperac-
tivity in central nervous neurotransmitter systems,
induces cellular changes that can be regarded as a form
of plasticity.This causes mood alterations in the affected
individual and has the potential to reverse the psy-
chopathological processes, thus alleviating the symptoms
of depression. Since social stress in animals evokes
symptoms that resemble those found in depressed
patients, chronic social stress can serve as an experi-
mental paradigm to investigate the neuronal processes
that may also occur during depressive disease in humans.
Research over past years has led to considerable
advances in the understanding of the neural causes of
depression and the cellular mechanisms that underlie the
beneficial effects of currently available antidepressants.
More importantly, such research forms the basis for the
future development of more effective antidepressant
drugs.
Stress changes the activity of noradrenergic
and adrenergic neurons
Stress is known to activate neurohormonal systems, such
as the hypothalamo-pituitary-adrenal (HPA) axis, to
release the central nervous stress peptide corti-
cotropin-releasing factor,
1
and to secrete glucocorticoids
from the adrenal gland.
2
These corticosteroids have been
identified as prominent factors that modify metabolic
processes in both the body and the brain during stress as
well as depression.
3
However, the other group of essen-
tial substances in basic and accelerated metabolism
includes the monoamines, noradrenaline, adrenaline,
1 7 1
P h a r m a c o l o g i c a l a s p e c t s
S
Copyright © 2004 LLS SAS. All rights reserved
www.dialogues-cns.org
Cellular consequences of stress and depression
Eberhard Fuchs, PhD; Gabriele Flügge, PhD
Stress is known to activate distinct neuronal circuits in
the brain and induce multiple changes on the cellular
level, including alterations in neuronal structures. On the
basis of clinical observations that stress often precipitates
a depressive disease, chronic psychosocial stress serves as
an experimental model to evaluate the cellular and mol-
ecular alterations associated with the consequences of
major depression. Antidepressants are presently believed
to exert their primary biochemical effects by readjusting
aberrant intrasynaptic concentrations of neurotransmit-
ters, such as serotonin or noradrenaline, suggesting that
imbalances within the monoaminergic systems con-
tribute to the disorder (monoaminergic hypothesis of
depression). Here, we review the results that comprise
our understanding of stressful experience on cellular
processes, with particular focus on the monoaminergic
systems and structural changes within brain target areas
of monoaminergic neurons.
© 2004, LLS SAS
Dialogues Clin Neurosci
. 2004;6:171-183.
Keywords:
noradrenaline; adrenaline; serotonin; dopamine; histamine; neuro
nal remodeling;
2
-adrenoceptor; 5-HT
1A
receptor; dopamine transporter; tree shrew
Author affiliations:
Clinical Neurobiology Laboratory, German Primate
Center, Göttingen, Germany
Address for correspondence:
Eberhard Fuchs, PhD, Clinical Neurobiology
Laboratory, German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany
(e-mail: efuchs@gwdg.de)