Difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC; 200-800 mg/kg, s.c.), to rats has no detectable behavioral effects using a battery of tests to assess sensorimotor function. In contrast, the induction of tremor by chlordecone, a neurotoxic agent that affects neuronal ionic processes, is significantly attenuated by pretreatment with DFMO. The effects of DFMO on chlordecone-induced tremor were reversed by pretreatment with putrescine. DFMO had no effects on p,p'-DDT, a tremorigen having a mechanism of action different from chlordecone. These findings imply that polyamines may play a role in select neuronal processes.

Unilateral injection of colchicine into the dentate gyrus, kainic acid into the CA3 pyramidal cell field, or cerebrospinal fluid into either site produced significant increases in ornithine decarboxylase (ODC) activity in both the injected and noninjected hippocampi. The magnitude as well as the time course of these changes varied with the cytotoxin, the site of injection, and whether or not animals had been pretreated with ganglioside GM1. The ganglioside regimen reduced the ODC response in the injected hippocampus but increased it on the side contralateral to the colchicine injection. In contrast, GM1 enhanced the ODC response produced by kainic acid in the injected but not the uninjected hippocampus. In a subsequent study morphometric analysis of the hippocampus revealed that pretreatment with GM1 did not alter the extent of hippocampal injury induced by either cytotoxin. These data indicate that the changes in ODC activity observed following hippocampal damage represent a complex set of biochemical changes that might serve to protect primary or secondary sites of insult and/or to promote either adaptive or maladaptive neural reorganization. Ganglioside GM1 altered the ODC response without minimizing the histopathological changes induced by the cytotoxins. The role of polyamines in neural, behavioral, and synaptic plasticity is currently under study.