Effect of prenatal and neonatal chronic exposure to phenobarbital on central and peripheral benzodiazepine receptors.
Phenobarbital (PhB) was administered to pregnant mice during days 9-18 of gestation. [3H]Muscimol binding to cerebellum, [3H]flunitrazepam binding to cerebellum and olfactory bulb, and [3H]PK 11195 binding to olfactory bulb, heart and kidney were assay in the of offspring at 22 and 50 days of age. The chronic prenatal administration of PhB did not affect either gamma-aminobutyric acid (GABA) receptors, central benzodiazepine receptors (CBR), or peripheral benzodiazepine binding sites (PBS) in these tissues. In the next stage of the study, we investigated a possible modulatory effect of chronic postnatal PhB treatment during days 2-21 of age on the same receptors measured at 22 and 50 days of age. PhB exposure of neonates resulted in a significant down-regulation of GABA receptors and CBR in the cerebellum and of PBS in the heart. The effects were demonstrated on day 22 of age and were undetectable by day 50 of age. CBR at the olfactory bulb and PBS at the olfactory bulb and kidney were not altered by the drug treatment. It is concluded that in utero exposure to PhB does not affect benzodiazepine receptor ontogenesis, and the effects of postnatal treatment are transitory only.
Fares
F
F
Department of Pharmacology, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
Weizman
A
A
Pick
C G
CG
Yanai
J
J
Gavish
M
M
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism*; D008297:Male; D051379:Mice; D009118:Muscimol / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011963:Receptors, GABA-A / Q000187:drug effects*
D011963:Receptors, GABA-A; D009118:Muscimol; D005445:Flunitrazepam; D010634:Phenobarbital