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

During adulthood, neuronal precursor cells persist in two discrete regions, the subventricular zone(19) and the hippocampal subgranular zone,(11) as r ecently demonstrated in primates.(10) To date, a few factors such as adrena l steroids(9) and trophic factors(13) are known to regulate adult neurogene sis. Since neuronal activity may also influence cellular development and pl asticity in brain, we investigated the effects of serotonin depletion on ce ll proliferation occurring in these regions. Indeed, in addition to its rol e as a neurotransmitter, 5-hydroxytryptamine (serotonin) is considered as a developmental regulatory signal.(14,22) Prenatal depletion in 5-hydroxytry ptamine delays the onset of neurogenesis in 5-hydroxytryptamine target regi ons(14) and 5-hydroxytryptamine promotes the differentiation of cortical an d hippocampal neurons.(15,23) Although in the adult brain, a few studies ha ve suggested that 5-hydroxytryptamine may play a role in neuronal plasticit y by maintaining the synaptic connections in the cortex and hippocampus,(3, 6,16) no information is actually available concerning the influence of 5-hy droxytryptamine on adult neurogenesis. If further work confirms that new ne urons 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-hy droxytryptamine on neurogenesis in the hippocampal formation, apart of the brain largely implicated in learning and memory processes. Indeed, lack of 5-hydroxytryptamine in the hippocampus has been associated with cognitive d isorders, such as depression, schizophrenia(1) and Alzheimer's disease.(7) In the present study, me demonstrated that both inhibition of 5-hydroxytryp tamine synthesis and selective lesions of 5-hydroxytryptamine neurons are a ssociated with decreases in the number of newly generated cells in the dent ate gyrus, as well as in the subventricular zone. (C) 1999 IBRO. Published by Elsevier Science Ltd.