The objective of this project is to account for the rapid changes in levels of ornithine decarboxylase (ODC) in tissues that respond to damage by regenerative or adaptive changes. The role of ODC is somewhat understood in relation to cell division but the function of this enzyme in non-proliferating tissues is unknown. Chlordecone administration to rats, at levels causing tremor (40 mg/kg body weight) causes a 21-24-fold increase in levels of adrenal ODC. This is a rapidly occuring, reversible event of much greater magnitude than any other biochemical response to chlordecone hitherto reported. The onset of chlordecone induced tremor can be prevented by pretreatment with an irreversible inhibitor of ODC, difluoromethylornithine (DFMO). This implies a relation between polyamines and behavioral responses. However, cerebral ODC levels are not markedly elevated in chlordecone-treated rats. Cerebral ODC is dramatically elevated following electroconvulsive shock or after intracerebral injections of colchicine or kainic acid. The regional specificity and time course of these effects are currently under study. The goals of this project are twofold: 1. Further understanding of the role of polyamines in the adult nervous system, especially in relation to neurotransmission. 2. The exploitation of the ODC assay in order to delineate the precise areas of the brain that may be initial targets of neurotoxic agents.
