BEHAVIORAL AND PHYSIOLOGICAL SEX-DIFFERENCES OBSERVED IN AN ANIMAL-MODEL OF FULMINANT HEPATIC-ENCEPHALOPATHY IN THE RAT

Hepatic encephalopathy is characterized by a number of neuropsychiatri c and motor disturbances observed in patients with liver dysfunction. The purpose of this study is to fully characterize behavioral and phys iological sex differences in an animal model of fulminant hepatic ence phalopathy (FHE). Male and female rats were administered thioacetamide (600 mg/kg) via i.p. (intraperitoneal) injection at Hours 0 and 24 an d allowed to progress into the four stages of FHE. Male rats reached a ll four stages of FHE significantly earlier than female rats (p < 0.05 ). The performance of thr male rats deteriorated more quickly (p < 0.0 5) than that of the females in all of the sensory and motor behavioral tests. Sex differences were observed in the liver enzymes of the FHE rats. The levels of aspartate aminotransferase (AST), alanine aminotra nsferase (ALT), and alkaline phosphatase were significantly greater (p < 0.05) in male rats in all four stages of FHE. Significant increases were also observed in the levels of direct and total bilirubin (p < 0 .05). Neuronal damage was observed in the CA(1) and CA(2) regions of t he hippocampus. In the CA(1) region, male rats displayed greater patho logical changes in Stages LU and IV (p < 0.05) than female rats. The d amage in the CA(2) region was only observed in Stage IV male rats. Our data indicate that observable behavioral and physiological sex differ ences occur in thioacetamide induced FHE in the rat. (C) 1997 Elsevier Science Inc.