para-Chlorophenylalanine induces lenticular opacities by prenatal, neonatal, and juvenile treatments, but not by adult treatment, in rats.

The lenticular opacities induced by the administration of para-chlorophenylalanine (PCPA) during the different developmental periods were investigated in rats. Rats were given PCPA (100 or 200 mg/kg) during prenatal, neonatal, juvenile, and adult periods, and their lenses were observed ophthalmologically. The prenatal treatment with PCPA on gestation days 14-20 (GD 14-20) produced lenticular opacities that were detected in the area of the lens nucleus (pin-head opacity), and the neonatal treatment on postnatal days 0-40 (PD 0-40) produced mature cataracts. The juvenile treatment on PD 14-40 produced opacities in the posterior area as early as the day following the first treatment (PD 15). When the administration was continued, mature cataract was developed. However, we did not detect any changes in the lens of the adult rat (over 11 weeks of age) treated with the same dose of PCPA. These results suggest that the incidence of a PCPA-induced cataract depends on the age of the animals when PCPA is administered.

Prenatal nicotine exposure affects the development of the central serotonergic system as well as the dopaminergic system in rat offspring: involvement of route of drug administrations.

The present study was undertaken to examine the effects of prenatal nicotine exposure by two different routes of drug administration, injection and infusion, on the development of monoaminergic systems and open field behavior in the neonatal and juvenile rat. The nicotine administration to pregnant Sprague-Dawley rats was carried out by subcutaneous injection (3 mg/kg twice daily) or infusion via implanted osmotic minipumps (6 mg/kg/day) from gestational day 4 (GD4) until GD20. At postnatal day 7 (PD7), 15 and 22, the contents of the neurotransmitters and their metabolites including noradrenaline (NA), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanilic acid (HVA), serotonin (5-HT) and 5-hydroxy-3-indolacetic acid (5-HIAA) were measured in the midbrain+pons - medulla (M + P - M), forebrain and cerebellum. Prenatal nicotine exposure caused a persistent reduction of DA turnover in the forebrain at PD15 and PD22. In addition, the 5-HT system was also affected by prenatal nicotine, and reductions of 5-HT turnover in the M + P - M at PD15 and in the forebrain and the cerebellum at PD22 were found. Although there was no effect of prenatal nicotine on NE contents, the involvement of this system remains uncertain since we measured only NE contents without metabolites. In the present study, we also found significant route-related changes in the contents of the monoamines and metabolites in the NA, DA and 5-HT systems in all brain regions in rat offspring besides the effects of prenatal nicotine. In addition, the difference in administration route reflected the results of the open field test and the number of ambulations in the injection-group was less than that in the infusion-groups with no relation to nicotine administration. Therefore, such effects of "prenatal stress" accompanied by drug administration are not negligible in considering the risk assessment of prenatal nicotine exposure.

Elevation of plasma aldosterone levels of tadpoles at metamorphic climax.

Plasma aldosterone concentrations in Rana catesbeiana tadpoles during metamorphosis were determined by radioimmunoassay. Aldosterone levels were relatively low (0.7-1.4 ng/ml) during pre- and prometamorphosis. At the onset of climax, aldosterone concentration increased markedly and reached a peak (10.9 ng/ml) at stage XXII. Subsequently, aldosterone levels declined and at the end of metamorphosis (stage XXV), the average concentration was 3.9 ng/ml plasma. Administration of ACTH elevated plasma aldosterone levels in hypophysectomized tadpoles. When hypophysectomized animals were kept in thyroxine (T4), plasma aldosterone concentrations also increased. Combined ACTH and T4 treatment caused a marked increase in plasma aldosterone concentration. The possible involvement of thyroid hormone in the elevation of plasma aldosterone during metamorphosis is discussed.

Corticoids augment nuclear binding capacity for triiodothyronine in bullfrog tadpole tail fins.

The effect of aldosterone and corticosterone on T3 binding to the nuclear fraction of the tail fin of bullfrog tadpoles was investigated in vitro. Both corticoids (10(-7) - 10(-5) M) added to the incubation medium increased T3 binding in a dose-dependent manner. The aldosterone-induced increase in T3-binding was blocked by cycloheximide, an inhibitor of protein synthesis, and actinomycin D, an inhibitor of RNA synthesis. Scatchard analysis revealed that 10(-6) M aldosterone and corticosterone increased the maximum binding capacity for T3 by 60 and 41%, respectively, and that the corticoids did not alter the value of the dissociation constant. The significance of the finding is discussed in relation to metamorphosis.