Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats.

During adulthood, neuronal precursor cells persist in two discrete regions, the subventricular zone and the hippocampal subgranular zone, as recently demonstrated in primates. To date, a few factors such as adrenal steroids and trophic factors are known to regulate adult neurogenesis. Since neuronal activity may also influence cellular development and plasticity in brain, we investigated the effects of serotonin depletion on cell proliferation occurring in these regions. Indeed, in addition to its role as a neurotransmitter, 5-hydroxytryptamine (serotonin) is considered as a developmental regulatory signal. Prenatal depletion in 5-hydroxytryptamine delays the onset of neurogenesis in 5-hydroxytryptamine target regions and 5-hydroxytryptamine promotes the differentiation of cortical and hippocampal neurons. Although in the adult brain, a few studies have suggested that 5-hydroxytryptamine may play a role in neuronal plasticity by maintaining the synaptic connections in the cortex and hippocampus, no information is actually available concerning the influence of 5-hydroxytryptamine on adult neurogenesis. If further work confirms that new neurons can be produced in the adult human brain as is the case for a variety of species, it is particularly relevant to determine the influence of 5-hydroxytryptamine on neurogenesis in the hippocampal formation, a part of the brain largely implicated in learning and memory processes. Indeed, lack of 5-hydroxytryptamine in the hippocampus has been associated with cognitive disorders, such as depression, schizophrenia and Alzheimer's disease. In the present study, we demonstrated that both inhibition of 5-hydroxytryptamine synthesis and selective lesions of 5-hydroxytryptamine neurons are associated with decreases in the number of newly generated cells in the dentate gyrus, as well as in the subventricular zone.