Effects of gestational exposure to phencyclidine: distribution and neurochemical alterations in maternal and fetal brain.
Phencyclidine is a widely used drug of abuse and is known to produce a wide variety of psychoactive effects. PCP abuse by pregnant women has been reported to result in the birth of infants exhibiting irritability, jitteriness and hyperactivity with high pitched cries. The present study was designed to evaluate the distribution of PCP in the maternal and fetal brain and the neurochemical effects produced by gestational exposure. Pregnant Sprague-Dawley rats were treated sc with 5 mg/kg PCP on 3 consecutive days (GD 9-11, 12-14, 15-16, or 18-20). On gestational day (GD) 21 all rats were killed by decapitation and maternal and fetal blood was collected for PCP analysis. Brains were dissected from dams and fetuses for PCP and neurochemical analyses. On GD 21 after exposure on GD 18-20, the fetal: maternal ratio of brain PCP concentrations was 11:1. PCP exposure on GD 12-14, 15-17, and 18-20 significantly decreased fetal brain PCP binding sites on GD 21, whereas maternal values were unchanged. Fetal dopaminergic and muscarinic cholinergic receptor binding and neurotransmitter concentrations were unaffected by prenatal PCP exposure. These data demonstrated that maternal PCP exposure resulted in prolonged exposure of the developing CNS and also indicated that gestational exposure to PCP decreased high affinity binding sites of PCP in term fetal brain.
Ali
S F
SF
Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079.
Ahmad
G
G
Slikker
W
W
Bondy
S C
SC
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development*; D001923:Brain Chemistry / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000502:physiology*; D005865:Gestational Age; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D010622:Phencyclidine / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011813:Quinuclidinyl Benzilate; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D017478:Receptors, Phencyclidine; D013134:Spiperone
D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D011976:Receptors, Muscarinic; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D013134:Spiperone; D011813:Quinuclidinyl Benzilate; D010622:Phencyclidine