Chlordecone (kepone) on the night of proestrus inhibits female sexual behavior in CDF-344 rats

The effect of the estrogen-like chlorinated pesticide chlordecone (Kepone) on sexual behavior was examined in proestrous rats following treatment with 25, 50, or 75 mg/kg chlordecone. In most animals, sexual behavior, both receptivity and proceptivity, was reduced within 60 min following the higher dosage of chlordecone. Reduced sexual receptivity occurred more slowly with 50 mg/kg chlordecone (usually within 180 min) and no reduction was seen following 25 mg/kg chlordecone. The reduced sexual behavior after chlordecone treatment preceded the onset of marked chlordecone-induced tremor. A group of rats treated with 75 mg/kg chlordecone was euthanized at the time that behavioral inhibition began to develop. The content of serotonin, norepinephrine, and their principal metabolites was determined by high-performance liquid chromatography of extracts of brain tissue of these animals. In hypothalamus, increases in serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) content, and a decrease in the level of norepinephrine (NE), were detected in chlordecone-treated rats relative to matched controls which received vehicle. The content of 5-HT was also increased in preoptic area of chlordecone-treated females. The content of the catecholamine metabolite, 3,4-dihydroxy-phenylacetic acid, was unaffected by chlordecone in either part of brain. These are the first observations of the parallel effects of chlordecone on receptive and proceptive behaviors, and on neurochemistry, in female rats; the results demonstrate short-latency effects of the pesticide treatment on the CNS events that mediate female reproductive behavior. Results of previous studies had led to the suggestion that chlordecone's inhibition of sexual behaviors resulted from its interaction with the intracellular estrogen receptor. However, the rapidity of the inhibition during the period of ongoing sexual behavior makes it unlikely that the inhibition is mediated by the pesticide's action at the intracellular estrogen receptor. Because of the importance of sexual behaviors to reproductive fitness, the current results indicate that nonsteroidal, behavioral mechanisms could contribute to chlordecone's neuroreproductive toxicity.