Brain neurotransmitter receptor alterations in offspring of rats exposed to phenobarbital, phenytoin or their combination during pregnancy.
Neurotransmitter receptor binding was studied in the progeny of rats exposed to phenobarbital (80 mg/kg), phenytoin (80 mg/kg) or their combination daily from 5 to 20 days of gestation. At 22 days postnatally, female pups in all treated groups showed decreased binding of [3H]spiroperidol to striatal membranes. A decreased binding of [3H]diazepam to frontal cortical membranes was observed in the female pups of rats exposed to phenytoin or the combination. The Scatchard analysis of data from the affected groups revealed a decrease in the maximum number of dopamine and benzodiazepine receptor sites and no change in their affinities. The binding of [3H]spiroperidol or [3H]diazepam was not altered significantly in any of the drug-treated male pups. Also, no significant change in the binding of [3H]serotonin or [3H]quinuclidinyl benzilate to frontal cortical membranes was observed in any of the treated groups. At 60 days postnatally, no significant change in the binding of any of the above ligands was evident. The above prenatal drug exposures appear to cause transitory subsensitivity of dopamine and benzodiazepine receptors in rats.
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D010634:Phenobarbital / Q000008:administration & dosage / Q000633:toxicity*; D010672:Phenytoin / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism
D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D013134:Spiperone; D010672:Phenytoin; D003975:Diazepam; D010634:Phenobarbital