Electron microscopic studies on the cerebral lesions of rats in experimental chronic disulfiram poisoning.

Following chronic administration of disulfiram to rats, changes of the brain were examined electron-microscopically. Pathological findings were observed in the nerve cells of the cerebral cortex and hypothalamus at later stage and synaptic changes in the hypothalamus from initial stage. On the other hand, changes of myelinated fibers, neuroglias and capillaries were very slight. It was considered that neurons were affected more predominantly than other neuronal elements by the cytotoxic action of the drug, and that the synaptic changes of the hypothalamus might reveal chronic disturbance of noradrenergic transmission by inhibition of dopamine-beta-hydroxylase. These ultrastructural findings might relate to the pathogenic mechanism of the disulfiram psychosis.