Chronic cocaine exposure in the fetal rhesus monkey: Consequences for early development of dopamine neurons

Oline K. Ronnekleiv, Barry R. Naylor

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

The effects of cocaine on the development of neurons containing tyrosine hydroxylase (TH) were investigated in fetal rhesus macaques. Pregnant monkeys were treated with cocaine 3 mg/kg or saline i.m., four times a day from day 18 of pregnancy until days 40 or 60. Cocaine concentration in plasma from females thus treated was approximately 800 ng/ml 10-20 min following injection. At the time of C-section, plasma levels of cocaine in fetal blood were 231 ± 70 ng/ml. The brains from 40 and 60 d old fetuses were examined using immunocytochemistry and in situ hybridization. The appearance of neurons containing TH by day 40 of gestation was not different between control and cocaine-treated fetal monkeys. In both groups (N = 3 each) TH-IR neurons and TH mRNA were located in the mesencephalon and dorsal hypothalamus by day 40, and fiber projections extended to the developing striatum. Also in the day 60 fetuses, the TH-IR neurons were distributed similarly in both groups (N = 5 each), but the TH mRNA content, measured by quantitative in situ hybridization, was reduced in the substantia nigra (SN) end ventral tegmental area (VTA) after cocaine treatment. These data suggest that exposure to cocaine in fetal life does not affect the development of TH or the expression of its mRNA on day 40 of gestation. By day 60, however, the expression of TH mRNA was significantly reduced. This latter effect can be explained by reduced dopamine synthesis in the cocaine-treated fetuses.

Original languageEnglish (US)
Pages (from-to)7330-7343
Number of pages14
JournalJournal of Neuroscience
Volume15
Issue number11
DOIs
StatePublished - Nov 1995

Keywords

  • cocaine
  • dopamine neurons
  • fetal monkey
  • immunocytochemistry
  • in situ hybridization
  • mesencephalon
  • tyrosine hydroxylase

ASJC Scopus subject areas

  • Neuroscience(all)

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