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Fiscal Year 2004 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 2003 : ¥2,600,000 (Direct Cost : ¥2,600,000)
We investigated the effects of perinatal exposure to bisphenol A(BPA), an endocrine disrupter on the development of amygdaloid kindling in developing rats.
(1)BPA (10 mg/kg) was administered orally to mother rats from gestation day(GD) 12 through postnatal day(PND) 10. Estradiol benzoate(EB) (20 μg/g) was subcutaneously injected to rats on PND 1,3,5,7 and 9. BPA treatment increased significantly the number of stimulations to reach the first stage 5 seizure (kindling rate) in pups on PND 14, while decreased the kindling rate on PND 70. However, EB treatments decreased the kindling rate on both PND 14 and 70.
(2)After implantation of bipolar electrodes in amygdala, effects of BPA and EB on electrical kindling acquisition were investigated by daily intraperitoneal injection of BPA (1,4,10 mg/kg) or EB (10,50,100 μg/kg) in different groups of male rats. BPA failed to produce any significant effect, but EB at dose of 50 μg/kg decreased significantly the kindling rate.
(3)After the completion o
f amygdaloid kindling, fully kindled male rats were treated with voirous doses of BPA (1,2,10 mg/kg) or EB (10,30,100 μg/kg), and kindled seizure parameters such as seizure stage, after-discharge duration(ADD) were recorded at various times (30 and 90 min) compared with the kindling parameters before treatment of BPA or EB. BPA failed to produce any effect, while 30- μg/kg dose of EB produced a significant increment of ADDs (after 90 min).
(4)BPA (10 mg/kg) was administered orally to mother rats from gestation day(GD) 12 through postnatal day(PND) 10. Estradiol benzoate(EB)(20 μg/g) was subcutaneously injected to rats on PND 1,3,5,7 and 9. Rats treated with BPA or EB were tested in the open-field for 5 min on PND 10 and 70. BPA failed to produce any effect on the behavior. However, EB treatments reduced activity on PND 70. In addition, both BPA and EB treatments significantly reduced body weight of both male and female rats on PND 10,30, and 60. In addition, EB treatments reduced significantly testis weight in males on PND 80, but BPA did not affect the testis weight.
These results suggest that perinatal exposure to endocrine disrupters modified the seizure susceptibility of amygdaloid kindling in rats, while the effects of BPA were different from those of EB. Less