UC Irvine

Adult male rats receiving 10 or 30 ppm chlordecone (Kepone) in the diet for 90 days exhibited decreased binding of [3H]spiroperidol in membranes prepared from the striatum. [3H]Muscimol and [3H]quinuclidinyl benzilate binding in the cerebellum were also depressed. The binding of [3H]diazepam and [3H]serotonin to cortical membranes was unaltered in treated animals. The areas of brain of exposed animals which exhibited a reduced ability to bind several ligands for specific neurotransmitter-receptor sites also possessed an increased amount of membrane protein. The frontal cortex of chlordecone-dosed rats where ligand binding was not altered, showed no significant change in membrane protein content. Thus chlordecone-induced alterations in receptor properties could be accounted for in terms of a region-specific hyperplastic increase in nonreceptor proteins. Thirty days after cessation of dosing ligand-binding properties and membrane protein from regions of treated animals did not differ significantly from controls, suggesting that these effects were reversible at the dose levels used. Male and female rats exposed indirectly throughout gestation and lactation showed no abnormal concentrations of membrane protein at 30 days of age after a maternal diet of 1 or 6 ppm chlordecone. No decrease in cerebellar binding of muscimol or quinuclidinyl benzilate, in frontal cortical binding of serotonin, or in striatal binding of spiroperidol was observed. At the 6-ppm dose level, male rats had an elevation of striatal dopamine binding. These data illustrate that gestational exposure to chlordecone can have effects that are in an opposite direction than those observed after exposure of adults to a higher dose level. © 1981.