Effects of tri‐o‐tolyl phosphate on rat brain catecholamine and indoleamine metabolism

Abstract

Sprague‐Dawley‐derived rats were fed doses of tri‐o‐tolyl phosphate (TOTP) via gavage. The dose levels and administration periods were established in previous experiments designed to assess clinical neuropathy using rats trained to walk on a rotorod apparatus fitted with an electrode floor. After intravenous injections of either [³H]tryptophan or [³H]tyrosine, whole‐rat‐brain homogenates were analyzed, using liquid scintillation and spectrofluorometric techniques, for specific activities and levels of endogenous brain amines and their metabolites. Serotonin, norephinephrine, and dopamine turnover rates were calculated using specific activities obtained at two different sacrifice time periods. Animals given 6 doses of 30–300 mg TOTP/kg body weight, administered every 3 d, showed slightly elevated, nonsignificant serotonin turnover rates, while levels of serotonin and tryptophan remained unchanged with a slight decrease in 4‐hydroxyindoleacetic acid levels at the highest dosages. Similarly treated animals showed no changes in endogenous levels of norepinephrine, dopamine, tyrosine, or 3,4‐dihydroxyphenylacetic acid, nor in turnover rates of norepinephrine or dopamine.