Alterations in biodistribution of cocaine may explain differential toxicity in pregnant and postpartum rats.
Biodistribution of cocaine in female rats before and after delivery of litters was studied in order to provide an explanation for the observed differences in cocaine-induced toxicity in pregnant and postpartum rats. Cocaine (20 mg/kg, ip) given to female rats at 16 days of gestation or 20 days of gestation did not have any apparent neurotoxic effects in the mothers. Similarly, no apparent toxicity was observed in virgin animals injected with the same dosage of cocaine. However, administration of the same dosage of cocaine to rats after delivery caused clonic-tonic convulsions and death within 5 min of injection. In an effort to explain these differences, the biodistribution of cocaine was investigated by injecting levo-[benzoyl-3,4-3H(N)] cocaine (20 mg/20 microCi/kg, ip) to nonpregnant rats and rats at different gestation periods and after delivery. The mean serum/brain ratios (concentration of cocaine in serum divided by cocaine concentration in the brain) of cocaine 5 min after injection in rats at 16 days gestation, 20 days gestation, within a 12-hr period after delivery, and in control virgin animals were 2099, 1132, 427, and 632, respectively. These results indicate that the biodistribution of cocaine is altered at parturition. This may explain the increased central nervous system toxicity in rats treated with cocaine after delivery. Results from this investigation may be useful in evaluating complications during labor and delivery which have been associated with cocaine abuse by pregnant women.
Dwivedi
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College of Pharmacy, South Dakota State University, Brookings 57007.
Engineer
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FN
Vaughan
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D000818:Animals; D001921:Brain / Q000378:metabolism; D003042:Cocaine / Q000493:pharmacokinetics* / Q000633:toxicity; D005260:Female; D005333:Fetus / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D049590:Postpartum Period / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D003042:Cocaine