Gestational exposure to phencyclidine (PCP) in rats decreases PCP binding sites in term fetal brain.
Pregnant Sprague-Dawley rats were treated with 5 mg/kg body weight of phencyclidine (PCP) injected at 1 ml/kg subcutaneously on three consecutive days at four different stages of gestation. Within 10-30 min after treatment, dams showed some lack of motor coordination and became lethargic. On gestational day 21, all rats were killed by decapitation and brains were dissected and stored from mother and fetus for neurochemical analysis. PCP, dopamine and muscarinic cholinergic receptor binding was measured in membranes prepared from maternal and fetal whole brain. Neurotransmitter concentrations were also measured in the fetal brain homogenates. There was a significant decrease in PCP binding sites in fetal but not maternal brains after maternal PCP injection at gestational days 12-14, 15-17 and 18-20, but not at 9-11 days. Dopamine and muscarinic cholinergic receptor binding was not significantly altered in fetal or maternal brain when compared with vehicle control animals. The whole brain dopamine, 3,4-dihydroxyphenylacetic acid, serotonin, and 5-hydroxyindoleacetic acid concentrations did not show significant change in any group studied. These data indicate that gestational exposure to PCP decreases high affinity binding of PCP in term fetal brain at doses which do not alter maternal PCP receptor binding.
Ali
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Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, AR 72079.
Ahmad
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Slikker
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Body
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D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D003597:Cytosine Nucleotides; D005260:Female; D005865:Gestational Age; D010622:Phencyclidine / Q000008:administration & dosage*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D017478:Receptors, Phencyclidine
D003597:Cytosine Nucleotides; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D010622:Phencyclidine