Tramadol administration induced hippocampal cells apoptosis, astrogliosis, and microgliosis in juvenile and adult male mice, histological and immunohistochemical study

Abstract

ABSTRACT Tramadol is a common analgesic, frequently used for relieving moderate or severe pain and widely used to delay ejaculation. However, repeated large doses have several adverse effects, especially on the brain tissue. So, this study was designed to assess the potentially deleterious effects of chronic administration of tramadol on principal fields of the hippocampus in adult and juvenile male albino mice. Thirty swiss male albino mice were divided equally into three groups: Group Ia (control adult) 3 months old, Group Ib (control juvenile) 3-week postnatal mice, Group II (tramadol treated adult mice) and Group III (tramadol treated juvenile mice). Both treated groups received tramadol tablets dissolved in water in a dose of 40mg/kg for 1 month by gastric tube. Tramadol treated groups showed degenerative changes in dentate gyrus (DG) granule cells, pyramidal neurons of CA1and CA3 fields in the form of electron-dense or rarified cytoplasm, dilated rER and mitochondrial changes. Additionally, immunohistochemical results revealed significantly increased in caspase 3 positive cells in different hippocampal principal fields. Astrogliosis and microgliosis were proved by the increased immunoreactivity of astrocytes to glial fibrillary acidic protein (GFAP) and microglia to CD68. Morphometric findings showed a significant reduction of both surface area of granule and pyramidal cells, and in thickness of DG, CA1, CA3 layers. Moreover, most of these morphological changes were aggravated in the juvenile-treated group. So, it can be concluded that tramadol abuse can induce an altered morphological change on the principal fields of the hippocampus in adult and juvenile mice.