The effects of lindane, DDT, and chlordecone on avoidance responding and seizure activity.

Male adult Fischer-344 rats were given various doses of lindane (0, 15, and 30 mg/kg, po), chlordecone (0, 25, 50, or 100 mg/kg, ip), or p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) (0, 25, 50, or 100 mg/kg, po) and tested for their ability to perform a two-way shuttle box task or to learn and retain a step-through passive avoidance response. Administration of p,p'-DDT or chlordecone 3 hr prior to acquisition did not affect the number of shuttle box avoidance responses made during a 60-trial training task, while responses during the intertrial interval (ITI) were decreased. Rats receiving 15 or 30 mg/kg of lindane made fewer avoidance responses, but did not differ from controls in terms of the number of responses during the ITI. When 30 mg/kg lindane was given 3 hr prior to passive avoidance acquisition, retention was impaired 7 days later; the lower dose of lindane, and all doses of chlordecone or p,p'-DDT had no effect under these conditions. When these chemicals were given immediately after passive avoidance training, animals treated with lindane were not affected. Animals receiving 100 mg/kg of p,p'-DDT or chlordecone displayed marked signs of toxicity and animals tested 7 days after training showed an impaired retention. Pretreatment with anticonvulsants such as phenobarbital and chlordiazepoxide, which may enhance GABA-mediated responses, blocked the disruptive effects of lindane (30 mg/kg) on shuttle box avoidance. The seizure-related activity produced by a higher dose of lindane (60 mg/kg) and kainic acid, a hippocampal excitotoxin, was also blocked by phenobarbital and chlordiazepoxide. Pretreatment with phenytoin, which is thought to bind to the inactivation gates of sodium, had no effect on the effects produced by lindane or kainic acid. These data suggest that treatment with nonconvulsant doses of lindane can interfere with the ability to acquire and use new information and that these effects may be associated with alterations in GABA.