Prenatal cocaine exposure and postnatal hypoxia independently decrease carotid body dopamine in neonatal rats.
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 ml/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 (FlO2). 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 FlO2 condition decreased DA compared to 0.21 FlO2. 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.
Lipton
J W
JW
Department of Neurological Sciences, Rush Medical College of Rush University, Rush Children's Hospital, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA.
Yuengsrigul
A
A
Ling
Z D
ZD
Weese-Mayer
D E
DE
Carvey
P M
PM
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002344:Carotid Body / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D000860:Hypoxia / Q000378:metabolism*; D009294:Narcotics / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D009294:Narcotics; D015102:3,4-Dihydroxyphenylacetic Acid; D003042:Cocaine; D004298:Dopamine