Antidepressants
cause increased neurogenesis in rat
hippocampus
Stress
and glucocorticoid activation provoke atrophy of
dendritic arborisation and reduced formation of
new neurones in the mammalian brain. The
consequence is a reduced volume of the
hippocampus in depressive disorders. In
contrast, stimuli such as exercise, hippocampus
dependent memory formation and learning
opportunities, estrogen and enhanced social
interaction increase neurogenesis. Studies have
demonstrated that administration of
antidepressants for 2 to 4 weeks enhances
neurogenesis in adult rat hippocampus through
the up-regulation of the cAMP signal
transduction cascade and the expression of brain
derived neurotrophic factor in the hippocamus.
The effects of stress on hippocampal neurones is
blocked or reversed by the up-regulation of
neurogenesis. Other studies in rodents have
shown that the administration of the selective
serotonin reuptake inhibitor, fluoxetine,
reverses the decrease in neurogenesis and
helplessness provoked by an inescapable
footshock. Although the hippocampus is not the
brain region directly influencing mood, its
connections with the amygdala and prefrontal
cortex could regulate emotional states. These
findings suggest that the regulation of
neurogenesis is possible in the normal, diseased
and injured brain and will allow new therapies
based on a better understanding of the
fundamental mechanisms triggering the
stress-related mood disorders. Neuropsychopharmacology
25: 836-844, 2001