Author

Craig H. Farr

Date of Award:

1992

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Animal, Dairy, and Veterinary Sciences

Advisor/Chair:

Raghubir P. Sharma

Abstract

Several industrial and environmental chemicals cause distal and/or central neuropathy among other diverse toxic effects. Spague-Dawley derived rats were fed doses of 2,5-hexanedione, acrylamide, tri-o-tolyl phosphate, leptophos and methylmercury 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 3H-Tryptophan, whole rat brain homogenates were analyzed using liquid scintillation and spectrofluorometric techniques for levels of tryptophan, serotonin and 5-hydroxyindoleacetic acid. Serotonin turnover rates were calculated using the specific activities of tryptophan and serotonin at two different time periods. The levels of serotonin as well as the serotonin turnover rates were unaffected by dosages of 5 to 50 mg acrylamide/kg given daily doses, while whole brain concentrations of 5-hydroxyindoleacetic acid increased significantly in a dose-dependent manner. the rise in 5-hydroxyindoleacetic acid levels coupled with no effects on the other levels in acrylamide and 2,5-hexanedione-fed animals suggests a possible inhibition of the energy-dependent 5-hydroxyindoleacetic acid efflux system in the brain. Animals given five doses of Leptophos (4.5 to 45 mg/kg) or six doses from 30 to 300 mg/kg tri-o-tolyl phosphate, administered every third day, showed slightly eleveated, non-significant, serotonin turnover rates while levels of serotonin and tryptophan remained unchanged with a slight decrease in 5-hydroxyindoleacetic acid levels at the highest dosages. Levels of endogenous indole compounds in methylmercury treated rats showed no significant differences from control values; however, the turnover rates and levels of serotonin were slightly lower in the two lower treatment levels, while the highest dose level had no apparent effect on turnover rates or concentrations. Further studies involving longer treatment periods, alternate species or examination of discrete brain areas, may further clarify the effects of these chemicals on brain biochemistry.

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