Prenatal cocaine exposure reduces glial cell line-derived neurotrophic factor (GDNF) in the striatum and the carotid body of the rat: Implications for DA neurodevelopment

Jack W. Lipton*, Zaodung Ling, Toan Q. Vu, Heather C. Robie, Kile P. Mangan, Debra E. Weese-Mayer, Paul M. Carvey

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Glial cell line-derived neurotrophic factor (GDNF) is a glycosylated, disulfide-bonded homodimer, and a member of the transforming growth factor- beta superfamily. GDNF has been shown to promote the survival and morphological differentiation of dopamine (DA) neurons and increase their high-affinity dopamine uptake. In order to determine whether the mechanism for our previously observed cocaine-induced DA reductions in brain and carotid body were GDNF-mediated, we exposed Sprague-Dawley rat fetuses to cocaine via maternal subcutaneous injections (30 mg/kg b.i.d., E7-E19). Brains and carotid bodies of fetuses were excised and processed for assessment of GDNF levels using an Enzyme-Linked ImmunoadSorbent Assay (ELISA). ANOVA indicated that cocaine reduced carotid body GDNF by 36% (F((1,5)) = 28.11, p < 0.05) and striatal GDNF by 41% (F((1,5)) = 41.77, p < 0.01). Although there was no interaction between drug exposure and fetal uterine position, post-hoc pairwise comparisons indicated that reductions in GDNF in the cocaine groups were due to differences at more distal positions (positions 4-8). The magnitude of the reductions in striatal GDNF (but not carotid body GDNF) in both cocaine-exposed and control fetuses followed a cervical (smallest GDNF reductions) to ovarian (greatest GDNF reductions) uterine position gradient. This pattern was similar to that which we observed in prior studies examining DA reductions in brain following prenatal cocaine exposure. The finding that cocaine reduces GDNF levels in striatum and carotid body support the hypothesis that cocaine's ability to reduce striatal and carotid body DA may be indirect through its ability to reduce GDNF. These data along with previous findings support the hypothesis that cocaine's effects on DA neurons are at least partially due to its indirect effects on trophic activity. The possible mechanisms whereby cocaine affects trophic activity are discussed.

Original languageEnglish (US)
Pages (from-to)231-235
Number of pages5
JournalDevelopmental Brain Research
Volume118
Issue number1-2
DOIs
StatePublished - Dec 10 1999

Keywords

  • Carotid body
  • Cocaine
  • Dopamine
  • ELISA
  • Embryonic brain
  • Glial cell

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology

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