TCDD DECREASES BRAIN INOSITOL CONCENTRATIONS IN THE RAT

A single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduced significantly brain regional inositol levels in both the most TCDD-susceptible (Long-Evans; LD(50) 9.8 mu g/kg and the most TCDD-resistant (Han/Wistar; LD(50) > 7200 mu g/kg) rat strain. The decrease emerged earlier in Long-Evans rats but was similar in magnitude al 8 days in both strains. There were some inconsistent and largely dose-independent changes in inositol-1- and inositol-4-monophosphate concentrations at 2 days. On day 8, a tendency towards reduced levels was seen especially in H/W rats. We conclude that TCDD reduces brain inositol levels presumably by inhibiting its synthesis by way of substrate deficit (hypoglycemia), but this effect does not appear to be causally related to the lethal action of TCDD.