Fluoxetine enhances cell proliferation and prevents apoptosis in dentate gyrus of maternally separated rats

The mother-infant relationship is an instinctive phenomenon, and loss of ma ternal care in early life influences neonatal development, behavior and phy siologic responses.(1,2) Furthermore, the early loss may affect the vulnera bility of the infant to neuropsychiatric disorders, such as childhood anxie ty disorders, personality disorders and depression, over its lifespan.(3,4) Fluoxetine is prescribed worldwide for depression and is often used in the treatment of childhood mental problems related to maternal separation or l oss of maternal care.(5,6) In the present study, fluoxetine was administrat ed to rats with maternal separation to determine its effects on neuronal de velopment, in particular with respect to cell proliferation and apoptosis i n the dentate gyrus of the hippocampus. Rat pups were separated from their mothers and socially isolated on postnatal day 14 and were treated with flu oxetine (5 mg kg(-1)) and 5-bromo-2'-deoxyuridine (BrdU) (50 mg kg(-1)) for 7 days, after which immunohistochemistry and a terminal deoxynucleotidyl t ransferase-mediated dUTP nick-end labeling (TUNEL) staining were carried ou t. In the pups with maternal separation treated with fluoxetine, the number of BrdU-positive cells was significantly increased and that of TUNEL-posit ive cells was significantly decreased in the dentate gyrus compared to pups with maternal separation that did not receive fluoxetine treatment. These findings indicate that fluoxetine affects new cell proliferation and apopto sis, and we propose that fluoxetine may be useful in the treatment of mater nal separation-related diseases.