Prenatal cocaine exposure and postnatal hypoxia independently decrease carotid body dopamine in neonatal rats

Jack W. Lipton; Anchalee Yuengsrigul; Zao Dung Ling; Debra E. Weese-Mayer; Paul M. Carvey

doi:10.1016/S0892-0362(96)90027-6

Prenatal cocaine exposure and postnatal hypoxia independently decrease carotid body dopamine in neonatal rats

Jack W. Lipton, Anchalee Yuengsrigul, Zao Dung Ling, Debra E. Weese-Mayer^*, Paul M. Carvey

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

The effects of prenatal cocaine exposure on the levels of carotid body dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were investigated in 5-day-old rat pups exposed to normoxic and hypoxic conditions. Timed-pregnant Sprague-Dawley rats were injected b.i.d. with either cocaine HCl (30 mg/kg) or isotonic saline (1 mg/kg) from gestational days 7-21. On the fifth postnatal day, pups were subjected to either 20 min of 0.21. or 0.08 fractional inspired oxygen (F(I)O₂) Under a strictly timed protocol, both carotid bodies were removed from each pup, placed in an antioxidant solution to prevent DA breakdown, and subsequently analyzed via HPLC with electrochemical detection to determine carotid body DA and DOPAC content. Two-way ANOVA revealed decreases in DA in cocaine-exposed pups. No HVA was detectable in any of the samples. The 0.08 F(I)O₂ condition decreased DA compared to 0.21 F(I)O₂. The additive consequences of DA depletion resulting from the combination of prenatal cocaine and postnatal hypoxia decreased carotid body DA to 14% of control levels, with several animals exhibiting DA content below detection limits. Considering the role of the carotid body in the ventilatory response to hypoxia, these data suggest that prenatal cocaine exposure may adversely affect the normal chemoreceptive function of the carotid body.

Original language	English (US)
Pages (from-to)	283-287
Number of pages	5
Journal	Neurotoxicology and Teratology
Volume	18
Issue number	3
DOIs	https://doi.org/10.1016/S0892-0362(96)90027-6
State	Published - 1996

Funding

This research was funded in part by grants from the United Parkinson’s Foundation (P.M.C.) and the National Institute on Drug Abuse (DA 0.5730,J .W.L.). The authors would like to thank Colleen M. Buhrfiend, B.S., for her technical assistance and the National Institute on Drug Abuse Research Drug Supply System for supplying the cocaine HCl used in these experiments.

Keywords

DOPAC
In utero cocaine
Teratogenic effects
Ventilationb

ASJC Scopus subject areas

Cellular and Molecular Neuroscience
Developmental Neuroscience
Toxicology

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10.1016/S0892-0362(96)90027-6

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title = "Prenatal cocaine exposure and postnatal hypoxia independently decrease carotid body dopamine in neonatal rats",

abstract = "The effects of prenatal cocaine exposure on the levels of carotid body dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were investigated in 5-day-old rat pups exposed to normoxic and hypoxic conditions. Timed-pregnant Sprague-Dawley rats were injected b.i.d. with either cocaine HCl (30 mg/kg) or isotonic saline (1 mg/kg) from gestational days 7-21. On the fifth postnatal day, pups were subjected to either 20 min of 0.21. or 0.08 fractional inspired oxygen (F(I)O2) Under a strictly timed protocol, both carotid bodies were removed from each pup, placed in an antioxidant solution to prevent DA breakdown, and subsequently analyzed via HPLC with electrochemical detection to determine carotid body DA and DOPAC content. Two-way ANOVA revealed decreases in DA in cocaine-exposed pups. No HVA was detectable in any of the samples. The 0.08 F(I)O2 condition decreased DA compared to 0.21 F(I)O2. The additive consequences of DA depletion resulting from the combination of prenatal cocaine and postnatal hypoxia decreased carotid body DA to 14% of control levels, with several animals exhibiting DA content below detection limits. Considering the role of the carotid body in the ventilatory response to hypoxia, these data suggest that prenatal cocaine exposure may adversely affect the normal chemoreceptive function of the carotid body.",

keywords = "DOPAC, In utero cocaine, Teratogenic effects, Ventilationb",

author = "Lipton, {Jack W.} and Anchalee Yuengsrigul and Ling, {Zao Dung} and Weese-Mayer, {Debra E.} and Carvey, {Paul M.}",

note = "Funding Information: This research was funded in part by grants from the United Parkinson{\textquoteright}s Foundation (P.M.C.) and the National Institute on Drug Abuse (DA 0.5730,J .W.L.). The authors would like to thank Colleen M. Buhrfiend, B.S., for her technical assistance and the National Institute on Drug Abuse Research Drug Supply System for supplying the cocaine HCl used in these experiments.",

year = "1996",

doi = "10.1016/S0892-0362(96)90027-6",

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AU - Yuengsrigul, Anchalee

AU - Ling, Zao Dung

AU - Weese-Mayer, Debra E.

AU - Carvey, Paul M.

N1 - Funding Information: This research was funded in part by grants from the United Parkinson’s Foundation (P.M.C.) and the National Institute on Drug Abuse (DA 0.5730,J .W.L.). The authors would like to thank Colleen M. Buhrfiend, B.S., for her technical assistance and the National Institute on Drug Abuse Research Drug Supply System for supplying the cocaine HCl used in these experiments.

PY - 1996

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N2 - The effects of prenatal cocaine exposure on the levels of carotid body dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were investigated in 5-day-old rat pups exposed to normoxic and hypoxic conditions. Timed-pregnant Sprague-Dawley rats were injected b.i.d. with either cocaine HCl (30 mg/kg) or isotonic saline (1 mg/kg) from gestational days 7-21. On the fifth postnatal day, pups were subjected to either 20 min of 0.21. or 0.08 fractional inspired oxygen (F(I)O2) Under a strictly timed protocol, both carotid bodies were removed from each pup, placed in an antioxidant solution to prevent DA breakdown, and subsequently analyzed via HPLC with electrochemical detection to determine carotid body DA and DOPAC content. Two-way ANOVA revealed decreases in DA in cocaine-exposed pups. No HVA was detectable in any of the samples. The 0.08 F(I)O2 condition decreased DA compared to 0.21 F(I)O2. The additive consequences of DA depletion resulting from the combination of prenatal cocaine and postnatal hypoxia decreased carotid body DA to 14% of control levels, with several animals exhibiting DA content below detection limits. Considering the role of the carotid body in the ventilatory response to hypoxia, these data suggest that prenatal cocaine exposure may adversely affect the normal chemoreceptive function of the carotid body.

AB - The effects of prenatal cocaine exposure on the levels of carotid body dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were investigated in 5-day-old rat pups exposed to normoxic and hypoxic conditions. Timed-pregnant Sprague-Dawley rats were injected b.i.d. with either cocaine HCl (30 mg/kg) or isotonic saline (1 mg/kg) from gestational days 7-21. On the fifth postnatal day, pups were subjected to either 20 min of 0.21. or 0.08 fractional inspired oxygen (F(I)O2) Under a strictly timed protocol, both carotid bodies were removed from each pup, placed in an antioxidant solution to prevent DA breakdown, and subsequently analyzed via HPLC with electrochemical detection to determine carotid body DA and DOPAC content. Two-way ANOVA revealed decreases in DA in cocaine-exposed pups. No HVA was detectable in any of the samples. The 0.08 F(I)O2 condition decreased DA compared to 0.21 F(I)O2. The additive consequences of DA depletion resulting from the combination of prenatal cocaine and postnatal hypoxia decreased carotid body DA to 14% of control levels, with several animals exhibiting DA content below detection limits. Considering the role of the carotid body in the ventilatory response to hypoxia, these data suggest that prenatal cocaine exposure may adversely affect the normal chemoreceptive function of the carotid body.

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JO - Neurotoxicology and Teratology

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IS - 3

ER -

Prenatal cocaine exposure and postnatal hypoxia independently decrease carotid body dopamine in neonatal rats

Abstract

Funding

Keywords

ASJC Scopus subject areas

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