Makatsori A, Michal Dubovicky, Eduard Ujhazy, Bakos Jan, Jezova D
Laboratory of Pharmacological Neuroendocrinology, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, Bratislava, 83306, Slovakia.
Neurotoxicol Teratol. 2005 May-Jun;27(3):509-14. doi: 10.1016/j.ntt.2005.01.012. Epub 2005 Feb 19.
Neuroendocrine changes in fetal hydantoin syndrome have not been described yet. This study was aimed to verify the hypothesis that prenatal exposure to phenytoin influences the stress response of adult female offspring in an animal model. To study possible development of depression like state, hedonic behavior and long-term changes in neuropeptide gene expression in the hypothalamus were investigated. Treatment consisted of per os administration of 150 mg/kg of phenytoin or water daily, from day 7-18 of gestation. Adult female offspring (6 animals per group) were acutely stressed by 1 min handling. Blood was collected in conscious rats via tail artery cannulas before, 1, 15 and 30 min after the handling. Exposure to phenytoin in uterus resulted in increased catecholamine and corticosterone concentrations in response to a mild stressor of 1 min handling in adult offspring. The gestational treatment used in this study did not induce a depression like state nor long-term changes in neuropeptide gene expression in the adult offspring. In conclusion, prenatal exposure to phenytoin treatment enhanced the stress response of adult female offspring. Possible new component of fetal hydantoin syndrome is the increase in catecholamine release in response to a mild stressor in adulthood.
胎儿苯妥英综合征的神经内分泌变化尚未见报道。本研究旨在验证以下假设：在动物模型中，产前暴露于苯妥英会影响成年雌性后代的应激反应。为了研究类似抑郁状态的可能发展情况，对享乐行为以及下丘脑神经肽基因表达的长期变化进行了研究。从妊娠第7天至第18天，处理方式为每天经口给予150mg/kg苯妥英或水。成年雌性后代（每组6只动物）通过1分钟的处理进行急性应激。在处理前、处理后1分钟、15分钟和30分钟，通过尾动脉插管在清醒大鼠中采集血液。子宫内暴露于苯妥英会导致成年后代在受到1分钟处理的轻度应激源刺激时，儿茶酚胺和皮质酮浓度升高。本研究中使用的孕期处理并未在成年后代中诱导出类似抑郁的状态，也未引起神经肽基因表达的长期变化。总之，产前暴露于苯妥英处理增强了成年雌性后代的应激反应。胎儿苯妥英综合征可能的新成分是成年期对轻度应激源反应时儿茶酚胺释放增加。
