5,5-Diphenylhydantoin antagonizes neurochemical and behavioral effects of p,p'-DDT but not of chlordecone

Abstract

Rats were given 75 mg/kg of 5,5-diphenylhydantoin (phenytoin) or vehicle 30 min prior to 75 mg/kg of 1,1,1-trichloro-bis(p-chlorophenyl)ethane (p,p'-DDT) (p.o.) or chlordecone (i.p.) and tremor was measured 12 h later. Rats were then killed, and regional brain levels of biogenic amines and their acid metabolites and amino acids were determined. Pretreatment with phenytoin significantly attenuated the tremor produced by p,p'-DDT but enhanced that produced by chlordecone. p,p'-DDT had significant effects on the levels of aspartate, glutamate, 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), whereas chlordecone increased glycine, 5-HIAA, and MHPG levels. Pretreatment with phenytoin blocked p,p'-DDT-induced increases of aspartate in the brainstem and spinal cord, 5-HIAA in the hippocampus, and MHPG in the brainstem and hypothalamus. Phenytoin significantly enhanced chlordecone-induced increases of MHPG in the brainstem. These data indicate that organochlorine-induced increases in noradrenergic activity in the brainstem and spinal cord may be directly related to the tremorigenic effects of these chemicals.