COGNITIVE AND NEUROANATOMICAL EFFECTS OF TRIETHYLTIN IN DEVELOPING RATS - ROLE OF AGE OF EXPOSURE

Long-Evans rat pups were injected i.p. on postnatal day 5 (PND5) or 12 with 0, 3, or 5 mg/kg triethyltin sulfate (TET) and then tested on T- maze delayed alternation on PND21 or 28. Delayed alternation learning was impaired on PND21 and 28 in pups given 5 mg/kg TET. Pups given 5 m g/kg TET on PND5 were more impaired on delayed alternation than pups g iven 5 mg/ kg TET on PND12. Pups given 3 mg/kg TET on PND5 or 12 were unimpaired at either age of testing. On the day following training, pu ps were sacrificed for histological assessment employing Nissl- or imm unohistochemical staining for glial fibrillary acidic protein (GFAP), a putative marker of gliosis. Pups given 5 mg/kg TET on PND5 showed in creases in GFAP immunoreactivity (IR) in subiculum, amygdala, hippocam pus, piriform cortex, and entorhinal cortex with concomitant decreases in Nissl-stained cells in these regions. Pups given 5 mg/kg TET on PN D12 showed increases in GFAP IR in piriform cortex, amygdala and dorsa l hippocampus with concomitant decreases in Nissl-stained cells in the se regions. Exposure to 3 mg/kg TET on PND5 and PND12 produced a mild increase in GFAP IR in piriform cortex and amygdala but no discernible loss of Nissl-staining in these respective regions. TET-induced behav ioral deficits appear related to damage of structural correlates of th e human temporal lobe and not piriform cortical pathology. These resul ts demonstrate that the day of exposure greatly influences the magnitu de of the cognitive deficits and neuropathology associated with exposu re to TET. There appears to be a critical period during postnatal deve lopment for the developmental neurotoxicity of this compound.