Fluoxetine ameliorates adult hippocampal injury in rats after early maternal separation. A biochemical, histological and immunohistochemical study.

The mother-infant relation is important for brain development and maturation. To investigate hippocampus changes, we used 18 male rat pups from three dams. Pups were divided into a maternal care (control) group, a maternal separation (MS) group and a MS plus fluoxetine (MS + Fl) treated group. On postnatal day 22, pups were weaned and their serum corticosterone level measured. At 2 months, the hippocampus was removed and processed for histological, immunohistochemical and ultrastructural study. MS caused significant elevation of serum corticosterone level and a significant decrease in the thickness of the pyramidal and granular layers of the cornu ammonis 3 (CA3) and dentate gyrus (DG) areas of the hippocampus. Both CA3 and DG areas exhibited degenerative changes in nerve cells, which were shrunken with pyknotic nucleus and darkly stained cytoplasm. Electron microscopy showed condensed chromatin, degenerated mitochondria, cytoplasmic vacuoles and electron lucent cytoplasm with loss of most polyribosomes. Immunohistochemical staining showed significantly increased numbers of glial fibrillary acid protein-positive cells in the CA3 and DG, and numbers of Ki-67stained cells in the DG in the MS group compared to the control group. All adverse changes were ameliorated in the MS + Fl group. Our findings corroborate the importance of the mother-infant relation to hippocampal development and demonstrate a protective role for Fl in MS pups.