Prenatal cocaine exposure induces an attenuation of uterine blood flow in the rat.
We have previously demonstrated that maternal cocaine injections result in a gradient of fetal brain cocaine levels that decrease as a function of the fetuses' proximity to the ovaries at embryonic (E) day 15. Our prior data suggest that cocaine-induced vasoconstriction may (1) limit cocaine's entry into the brain and (2) cause damage to DA neurons through injury associated with hypoxia or ischemia of the utero-placental junction. Therefore, using the microsphere technique (labeled with Ru(103)), the following study sought to determine whether the previously observed pattern of cocaine distribution among fetuses in the uterus were due to position-specific reductions in uterine or placental blood flow. On day 15, a single subcutaneous injection of 30 mg/kg cocaine HCl was administered to each rat. Thirty minutes after the cocaine injection, reference blood samples were drawn from the ventral tail artery. Uterine segments and placentae were removed and subjected to gamma counting. While results regarding placental blood flow were equivocal, cocaine significantly reduced average uterine blood flow by 54.6%. In addition, as one moves more proximal to the ovaries, cocaine progressively attenuates blood flow in uterine tissue segments. These data support the hypothesis that the pattern of drug distribution and subsequent brain alterations from prenatal cocaine exposure in our previous reports are likely due to differences in uterine blood flow.
Lipton
Jack W
JW
Department of Pharmacology, Rush Medical College of Rush University, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA. jlipton@rush.edu
Vu
Toan Q
TQ
Ling
Zaodung
Z
Gyawali
Sandeep
S
Mayer
Jennifer R
JR
Carvey
Paul M
PM
D000818:Animals; D003042:Cocaine / Q000633:toxicity*; D005260:Female; D021041:Placental Circulation / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000633:toxicity*; D014662:Vasoconstrictor Agents / Q000633:toxicity*
D013723:Teratogens; D014662:Vasoconstrictor Agents; D003042:Cocaine