Early developmental exposure to benzodiazepine ligands alters brain levels of thiobarbituric acid-reactive products in young adult rats.
Levels of thiobarbituric acid (TBA)-reactive material were measured in brain regions of 3-4 month-old rats following prenatal exposure to several benzodiazepine (BDZ) receptor ligands over gestational days 14-20. Prenatal exposure to diazepam (DZ) at 1.0 mg/kg/day markedly elevated levels of brain TBA-reactive material while exposure to a higher dose (2.5 mg/kg) induced a significant increase only in the hippocampus. Early exposure to the central-type BDZ agonist clonazepam as well as to the central-type antagonist Ro 15-1788 also increased brain levels of TBA-reactive material. Concurrent exposure to the higher dose of DZ partially attenuated the effect of Ro 15-1788. Prenatal exposure to the peripheral-type BDZ ligand PK11195 produced a profound increase in TBA-reactive products in all regions, and concurrent DZ exposure did not attenuate this effect, except in the basal ganglia. Measurement of TBA-reactive material from birth to 3 months indicated that the effect of prenatal exposure to DZ was not apparent until after 8 weeks of age. Acute in vitro exposure of adult and fetal tissue to DZ had no effect on TBA-reactive material. The results suggest an interference in the organization of cellular metabolism in the brain by developmental exposure to BDZ ligands.
Miranda
R C
RC
Department of Psychology, University of Rochester, New York 14627.
Wagner
J P
JP
Kellogg
C K
CK
D000818:Animals; D001569:Benzodiazepines / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002998:Clonazepam / Q000008:administration & dosage; D003975:Diazepam / Q000008:administration & dosage*; D005260:Female; D005442:Flumazenil / Q000494:pharmacology; D005865:Gestational Age; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013858:Thiobarbiturates / Q000494:pharmacology*
D011963:Receptors, GABA-A; D013858:Thiobarbiturates; D001569:Benzodiazepines; D005442:Flumazenil; D002998:Clonazepam; C029684:thiobarbituric acid; D003975:Diazepam