The mother-infant relationship is an instinctive phenomenon, and loss of maternal care in early life influences neonatal development, behavior and physiologic responses. 1,2 Furthermore, the early loss may affect the vulnerability of the infant to neuropsychiatric disorders, such as childhood anxiety 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 loss of maternal care. 5,6 In the present study, fluoxetine was administrated to rats with maternal separation to determine its effects on neuronal development, in particular with respect to cell proliferation and apoptosis in the dentate gyrus of the hippocampus. Rat pups were separated from their mothers and socially isolated on postnatal day 14 and were treated with fluoxetine (5 mg kg −1 ) and 5-bromo-2Ј-deoxyuridine (BrdU) (50 mg kg −1 ) for 7 days, after which immunohistochemistry and a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining were carried out. In the pups with maternal separation treated with fluoxetine, the number of BrdU-positive cells was significantly increased and that of TUNELpositive 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 apoptosis, and we propose that fluoxetine may be useful in the treatment of maternal separation-related diseases. Molecular Psychiatry (2001) 6, 725-728.Rat pups were recruited on postnatal day (pnd) 14, and the pups were separated from their mothers and socially isolated throughout the duration of the following 1-week period for the following reasons. First of all, rat pups of 2 weeks of age are able to survive without their mothers, but they still show behavioral and physiological disturbances after a period of maternal separation. 2

Fluoxetine treatment during maternal separation enhances cell proliferation in the dentate gyrus. BrdU-immunostaining and methyl green counterstaining were done on sections obtained one day after the last day of the injections from each group; pups kept with their mothers (a) and pups with maternal separation (b), which have received daily injections of BrdU (50 mg kg −1 ) and saline, and fluoxetine-treated pups with maternal separation (c) which have received daily injections of BrdU (50 mg kg −1 ) and fluoxetine (5 mg kg −1 ). All injections were given for 7 days after postnatal day 14. n = 9 in each group. Scale bar represents 100 m. For further information on this topic, please see the article by HJ Lee et al on pages 725-728.

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