Acute exposure to tris(2-chloroethyl)phosphate produces hippocampal neuronal loss and impairs learning in rats

Abstract

Adult female. Fischer-344 rats were exposed to 275 mg/kg of tris(2-chloroethyl)phosphate (TRCP) by gavage. TRCP produced consistent signs of convulsive activity within 60–90 min after dosing and extensive loss of CA1 hippocampal pyramidal cells when examined 7 days after dosing. At the light microscopic level, toxic effects of TRCP on pyramidal cells in the CA3 and CA4 regions and on granule cells in the dentate gyrus were less severe than those on the CA1 cells. The seizure-related and neurohistological effects of TRCP were significantly attenuated by pretreatment with atropine or chlordizepoxide, suggesting that the hippocampal damage was related to the seizures produced by TRCP. In a second experiment designed to assess the potential health risk associated with TRCP, exposed rats were mildly impaired in the acquisition of a reference memory task in a water maze. However, TRCP-exposed rats were consistently impaired in performing a repeated acquisition task in the water maze. These data underscore the potential health risk associated with exposure to TRCP and support the conclusion that the hippocampus is intimately involved in spatial memory in rats.