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 monthold 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 attentuate 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.