Region-, age-, and sex-specific effects of fetal diazepam exposure on the postnatal development of neurosteroids.

Fetal exposure to diazepam (DZ), a positive modulator of GABA(A) receptors and an agonist at mitochondrial benzodiazine receptors, induces long-term neural and behavioral effects. This study evaluated whether the early manipulation influenced the normal development of brain levels of neurosteroids or altered steroid action at GABA(A) receptors. Pregnant dams were injected over gestation days 14 through 20 with DZ (2.

Effect of prenatal exposure to diazepam on brain GABA(A) receptor mRNA levels in rats examined at late fetal or adult ages.

This study tested the hypotheses that in utero exposure to diazepam (DZ): (1) exerts long-lasting effects on GABA(A) receptor function by altering GABA(A) receptor subunit mRNA levels in specific brain regions of adult animals and/or (2) alters GABA(A) subunit mRNA expression in exposed fetuses. We assayed levels of mRNAs encoding several of the most predominant GABA(A) receptor subunits as well as cyclophilin mRNA. Analysis of mRNA levels in the cortex in adults showed that only gamma2S mRNA levels varied significantly with prenatal drug exposure, an effect unrelated to DZ action to the GABA(A) receptor.

Sex-specific effects of in utero manipulation of GABA(A) receptors on pre- and postnatal expression of BDNF in rats.

Exposure to diazepam (DZ) during the last week of in utero development in rats induces neurobehavioral effects that do not become apparent in exposed animals until young adult ages. Some of the effects are sex specific. This study evaluated the hypothesis that late gestational exposure to DZ, a positive modulator of GABA(A) receptors, affects the developmental appearance of brain-derived neurotrophic factor (BDNF), an effect that could be linked to the later consequences of the exposure.

Neurosteroid action at the GABAA receptor in fetal rat forebrain.

In utero exposure to diazepam (DZ), a positive modulator of the GABAA (gamma-aminobutyric acid type A) receptor exerts profound effects on the offspring that become most apparent after the maturation of the brain during puberty and that are often sex specific, suggesting that the early exposure might have interfered with organizing actions of sex steroids. In addition to genomic actions, many reduced steroids interact directly with membrane receptors, including the GABAA receptor. In the present study, the effect of in vitro exposure to neurosteroids on GABA-stimulated 36chloride uptake in synaptoneurosomes from adult cerebral cortex or fetal forebrain (gestation day 20) was examined.

Importance of hypothalamic function to stressor-induced responsiveness of the GABAA receptor in the cerebral cortex: a non-corticosterone influence.

Catecholamine terminals in the paraventricular nucleus (PVN) of the hypothalamus of 60-day-old rats were destroyed by the stereotaxic injection of 6-hydroxydopamine into the PVN (6-OHDA; 9 micrograms/1.5 microliters bilaterally), and the rats were tested 2 weeks later. Lesions led to a 70% reduction of norepinephrine in the hypothalamus and a loss of dopamine-beta-hydroxylase immunoreactivity in the PVN.