Changes in the midbrain-rostral forebrain dopamine circuitry in the cocaine-exposed primate fetal brain

Oline Ronnekleiv, Yuan Fang, Wan S. Choi, Lin Chai

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

To ascertain cocaine's effects in the fetus, we developed a nonhuman primate model in which pregnant monkeys were administered cocaine (3 mg/kg im) or saline four times a day from day 20 through days 40-70 of a 165-day gestation. At the time of cesarean section, plasma levels of cocaine in fetal blood were 231 ± 70 ng/ml. Fetal brains were examined using immunocytochemistry, in situ hybridization, receptor autoradiography, and nuclease protection assay analysis. No differences were found in the expression of tyrosine hydroxylase and dopamine receptor mRNAs by days 40-45 of gestation. However, by day 60 the midbrain of monkeys exposed to cocaine had significantly reduced expression of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Moreover, dopamine D1 and D2 receptor mRNAs were significantly elevated in the rostral forebrain as were D1 and D2 receptor binding sites in days 60-70 cocaine-exposed fetuses. Cocaine treatment from day 20 to days 60 and 70 of gestation also significantly increased the mRNA concentrations of dynorphin and enkephalin in the rostral forebrain. These findings suggest that in utero cocaine exposure has profound effects on the developing dopamine neurocircuitry.

Original languageEnglish (US)
Pages (from-to)165-181
Number of pages17
JournalAnnals of the New York Academy of Sciences
Volume846
DOIs
StatePublished - 1998

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Prosencephalon
Mesencephalon
Cocaine
Primates
Dopamine
Brain
Tyrosine 3-Monooxygenase
Pregnancy
Messenger RNA
Haplorhini
Fetus
Nuclease Protection Assays
Dynorphins
Dopamine D1 Receptors
Dopamine D2 Receptors
Enkephalins
Dopamine Receptors
Autoradiography
Fetal Blood
Cesarean Section

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Changes in the midbrain-rostral forebrain dopamine circuitry in the cocaine-exposed primate fetal brain. / Ronnekleiv, Oline; Fang, Yuan; Choi, Wan S.; Chai, Lin.

In: Annals of the New York Academy of Sciences, Vol. 846, 1998, p. 165-181.

Research output: Contribution to journalArticle

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