Document Type

Thesis - University Access Only

Award Date

1996

Degree Name

Master of Science (MS)

Department / School

Pharmaceutical Sciences

First Advisor

Chandradhar Dwivedi

Abstract

Cocaine, a central nervous system stimulant, produces excitation, euphoria and restlessness in humans. In laboratory animals cocaine causes an increase in well-coordinated motor activity. As dosages are increased, cocaine produces tremors, seizures, and eventually clonic-tonic convulsions. Previous studies form this laboratory have indicated that cocaine at a dosage of 20 mg/kg administered intraperitoneally resulted in death due to clonic-tonic convulsions during the postpartum period in rats, but the same dosage was tolerated during pregnancy. The purpose of this investigation is to study the biodistribution of cocaine in pregnant rats during different perinatal periods and in nonpregnant female rats to understand the observed differential toxicity during the postpartum period. In this investigation, five groups of female rats were used, i.e., nonpregnant, 16 day pregnant, 21 day pregnant, 'within 4 hours after delivery' and 'within 24 hours after delivery'. Three to five rats were used for each time period of study as the sample size. Experiments were repeated in the case of questionable results. Cocaine (3H labeled) was combined with unlabeled cocaine and injected subcutaneously at the dosage of 20µCi/20mg/kg. Rats were anesthetized with ether and blood was collected by cardiac puncture at 5, 15, 30, and 60 minutes and 4, 12, and 24 hours after injection. The brain samples were collected from all the rats, and placenta and fetal brain samples were obtained from pregnant rats at 5, 15, 30, and 60 minutes and 4, 12 and 24 hours after injection. Serum was prepared by centrifugation of the blood. Accurately weighed (approximately 100 mg) tissue and serum (100µ1) samples were solubilized using a tissue solubilizer. The radioactivity of cocaine and radiolabeled metabolites in disintegrations per minute (dpm) was measured, and related to the distribution of cocaine levels in serum and tissue. Cocaine and radiolabeled metabolites were found to be distributed to placenta and fetal brain. The 21 day pregnant rat placenta and fetal brain cocaine and radiolabeled metabolites levels were significantly higher than those of 16 day pregnant rat placenta and fetal brain. The cocaine and radiolabeled metabolite levels in the placenta and fetal brain in both 16 day and 21 day pregnant rats were highest at the 4 hours after administration in this experiment. Similar results were also observed in maternal serum and brain. There were no significant differences among experimental groups after various time periods in maternal serum. The cocaine and radiolabeled metabolite levels in maternal brain in the postpartum group were significantly higher than 21 day, 16 day pregnant rats and nonpregnant rats. In the 24-hour postpartum group, maternal brain cocaine and radiolabeled metabolite levels were significantly higher than in the group examined 4 hours postpartum. The increased levels of cocaine and radiolabeled metabolite levels in the postpartum group may explain increased CNS toxicity during postnatal period. These results indicate that the brain levels of cocaine and radiolabeled metabolite in the "within 24 hours post delivery" group are significantly higher than the pregnant and nonpregnant groups. Based on these results it can be hypothesized that the volume of distribution changes during pregnancy and the postpartum period and increased levels of cocaine and radiolabeled metabolites are distributed into the brain during the postpartum period. The results further suggest that women who abuse cocaine during pregnancy and continue to abuse the same dose during the early postpartum period may endanger their lives.

Library of Congress Subject Headings

Rats -- Effect of drugs on
Rats -- Pregnancy
Cocaine
Drug abuse in pregnancy

Format

application/pdf

Publisher

South Dakota State University

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Rights Statement

In Copyright