THE MAGNITUDE OF BRAIN DOPAMINE DEPLETION FROM PRENATAL COCAINE EXPOSURE IS A FUNCTION OF UTERINE POSITION

Cocaine's teratogenicity remains equivocal in the literature, The vari ance in cocaine-induced teratogenic data led us to consider that the i ntrauterine exposure to cocaine is not homogenous and that sampling me thods presently utilized in the literature lead to inconsistent result s. Cocaine's vasoconstrictive actions, in concert with regional varian ce in the uterine milieu of the rodent, were postulated to differentia lly reduce the distribution of cocaine to fetal brains as a function o f uterine position. Fetuses in positions with the highest levels of co caine exposure were also hypothesized to have the most pronounced defi cits in whole brain dopamine (DA). The results indicated that whole br ain cocaine levels vary significantly in relation to a fetus' position in the uterine horn following a single SC injection of 30 mg/kg cocai ne HCl as measured by GC/MS. Brains of fetuses from the most proximal uterine position (in relation to the cervix) received an average of 32 9% of the cocaine of fetuses from the most distal uterine position, wh ereas no such relationship existed for amniotic fluid cocaine levels. Following exposure to cocaine from embryonic days 7 to 21, brain DA le vels were significantly reduced in distal fetuses relative to proximal fetuses and to distal controls. Contrary to the initial hypothesis, t he results indicated that the magnitude of cocaine exposure was invers ely related to the magnitude of DA reduction. Based upon findings in t he literature related to the uterine gradient of placental progesteron e distribution in the rat, cocaine's ability to lower brain DA levels was attributed primarily to its vasoconstrictive actions. Recommendati ons on how to statistically treat littermates, when foreknowledge of u terine position exists, are discussed. (C) 1998 Elsevier Science Inc.