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Changes in the Midbrain‐Rostral Forebrain Dopamine Circuitry in the Cocaine‐Exposed Primate Fetal Brain a
Author(s) -
RØNNEKLEIV OLINE K.,
FANG YUAN,
CHOI WAN S.,
CHAI LIN
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb09735.x
Subject(s) - forebrain , dopamine , endocrinology , tyrosine hydroxylase , medicine , prenatal cocaine exposure , midbrain , fetus , biology , catecholaminergic cell groups , gestation , dopamine receptor d1 , dopamine receptor , striatum , central nervous system , pregnancy , prenatal exposure , genetics
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 D 1 and D 2 receptor mRNAs were significantly elevated in the rostral forebrain as were D 1 and D 2 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.