The purpose of this research is to characterize the neurological effects of organochlorine compounds, including chlordecone, p,p'-DDT and lindane. A single exposure to lindane interfered with the learning and memory capabilities of rats, supporting the observation that lindane has effects on long-term potentiation in the hippocampus. Posttraining administration of lindane did not affect retention at a later time, indicating that the process of memory consolidation was not altered. Our results also indicate that chlordecone and p,p'-DDT have few consistent effects on learning and memory. Chlordiazepoxide and phenobarbital, which have effects on GABAergic function, attenuated lindane- induced seizure activity. These data are consistent with the observation that lindane is a competitive inhibitor at the picrotoxin binding site within the GABA receptor-ionophore complex. In other experiments, the neuropharmacological mechanism of chlordecone-induced hypothermia was determined. Initial studies found an association between chloredecone- induced hypothermia and cutaneous vasodilation. Subsequent experiments found that direct administration of chlordecone into the fourth, but not third or lateral ventricle, produced hypothermia. Chlordecone-induced hypothermia could be attenuated by administration of phenoxybenzamine or phentolamine, but not propranolol or atenolol, into the fourth ventricle. These data are consistent with the hypothesis that chlordecone causes the release of norepinephrine in the areas of the brain stem mediating peripheral vasomotor control. Activation of an alpha-1 adrenergic receptor in that area produces vasodilation, which may cause an increase in skin temperature and a decrease in core temperature. This is the final report of this program and no further work in this area is planned.
