Biodistribution of cocaine during perinatal period in rats.
Differences in cocaine-induced central nervous system toxicity in pregnant and postpartum rats have been observed. For example, a 20 mg/kg, intraperitoneal dosage of cocaine that was tolerated during pregnancy caused tonic-clonic convulsions and death during the postpartum period. In the present study, biodistribution of cocaine during different perinatal periods was investigated to understand the differences in toxicity. Nonpregnant, 22-day pregnant, and postpartum rats were injected with 3H cocaine (12 mg/20 mu ci/kg, i.v.). Rats were sacrificed under ether anesthesia at predetermined time intervals. Brain, serum, fetal brain and placenta (from pregnant rats) samples were isolated, solubilized, and counted in a scintillation counter for radioactivity. Peak levels of cocaine were observed at 15 and 60 minutes after injection in maternal serum and brain, respectively, in 22-day pregnant rats. However, peak levels of cocaine were observed at 30 minutes after the injection in placental and fetal brain tissues from 22-day pregnant rats. Cocaine level of brain was elevated in all postpartum rats compared to nonpregnant and pregnant rats. These results indicated that higher levels of cocaine is distributed to brain after delivery compared to the nonpregnant and pregnant rats which may explain increased CNS toxicity during postnatal period.
Dwivedi
C
C
Department of Pharmaceutical Sciences, College of Pharmacy South Dakota State University, Brookings 57007, USA.
Eighmy
A M
AM
Singh
K K
KK
D000818:Animals; D001923:Brain Chemistry; D003042:Cocaine / Q000493:pharmacokinetics* / Q000633:toxicity; D005260:Female; D005333:Fetus / Q000737:chemistry; D007275:Injections, Intravenous; D007743:Labor, Obstetric / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000737:chemistry; D049590:Postpartum Period / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D003042:Cocaine