The magnitude of brain dopamine depletion from prenatal cocaine exposure is a function of uterine position

Jack W. Lipton*, Heather C. Robie, Zaodung Ling, Debra E. Weese-Mayer, Paul M. Carvey

*Corresponding author for this work

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Cocaine's teratogenicity remains equivocal in the literature. The variance in cocaine-induced teratogenic data led us to consider that the intrauterine exposure to cocaine is not homogenous and that sampling methods presently utilized in the literature lead to inconsistent results. Cocaine's vasoconstrictive actions, in concert with regional variance in the uterine milieu of the rodent, were postulated to differentially reduce the distribution of cocaine to fetal brains as a function of uterine position. Fetuses in positions with the highest levels of cocaine exposure were also hypothesized to have the most pronounced deficits in whole brain dopamine (DA). The results indicated that whole brain cocaine levels vary significantly in relation to a fetus' position in the uterine horn following a single SC injection of 30 mg/kg cocaine HCl as measured by GC/MS. Brains of fetuses from the most proximal uterine position (in relation to the cervix) received an average of 329% of the cocaine of fetuses from the most distal uterine position, whereas no such relationship existed for amniotic fluid cocaine levels. Following exposure to cocaine from embryonic days 7 to 21, brain DA levels were significantly reduced in distal fetuses relative to proximal fetuses and to distal controls. Contrary to the initial hypothesis, the results indicated that the magnitude of cocaine exposure was inversely related to the magnitude of DA reduction. Based upon findings in the literature related to the uterine gradient of placental progesterone distribution in the rat, cocaine's ability to lower brain DA levels was attributed primarily to its vasoconstrictive actions. Recommendations on how to statistically treat littermates, when foreknowledge of uterine position exists, are discussed.

Original languageEnglish (US)
Pages (from-to)373-382
Number of pages10
JournalNeurotoxicology and Teratology
Volume20
Issue number4
DOIs
StatePublished - Jul 1 1998

Keywords

  • Dopamine
  • HPLC
  • In utero cocaine
  • Teratogenesis

ASJC Scopus subject areas

  • Toxicology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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