Ohta Ken-ichi, Sakata-Haga Hiromi, Fukui Yoshihiro
Department of Anatomy and Developmental Neurobiology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Congenit Anom (Kyoto). 2010 Jun;50(2):105-14. doi: 10.1111/j.1741-4520.2010.00269.x. Epub 2010 Feb 11.
It is known that the developing serotonergic system is one of the targets of ethanol teratogenicity. Because serotonin has multiple functions in both mature and immature brains, disturbance of the serotonergic system by ethanol exposure in utero can be cause of a wide range of psychiatric problems in adulthood. In the present study, we observed serotonergic neurons in the midbrain raphe nuclei and anxiety-like behaviors which would be affected by an altered serotonergic system in adult rats prenatally exposed to ethanol. Pregnant rats were fed a liquid diet containing 2.5-5.0% (w/v) ethanol on gestational days 10-21. Their offspring were examined at 60-70 days of age. A significant decrease in the number of serotonergic cells in the midbrain raphe nuclei was shown in prenatally ethanol-exposed offspring. In an open field test, they spent more time in a central area compared to controls. Also in an elevated plus maze test, prenatally ethanol-exposed offspring spent more time on the open arms than controls. These behavioral results suggested that prenatally ethanol-exposed rats were less sensitive to anxiety. However, 44% of prenatally ethanol-exposed offspring exhibited freezing behavior on the open arms of the elevated plus maze, causing strong anxiety, compared with 0% in intact control and 12.5% in isocaloric sucrose-fed control groups. These findings suggest that prenatal ethanol exposure decreases both susceptibility and resistance of anxiety. Insufficient serotonergic actions caused by reduced serotonergic neurons in the raphe nuclei might contribute to the alterations in anxiety-related behaviors observed in our prenatally ethanol-exposed rats.
已知发育中的血清素能系统是乙醇致畸作用的靶点之一。由于血清素在成熟和未成熟大脑中都有多种功能，子宫内乙醇暴露导致的血清素能系统紊乱可能是成年后出现各种精神问题的原因。在本研究中，我们观察了产前暴露于乙醇的成年大鼠中脑缝际核中的血清素能神经元以及可能受血清素能系统改变影响的焦虑样行为。怀孕大鼠在妊娠第10至21天喂食含2.5 - 5.0%（w/v）乙醇的液体饮食。它们的后代在60 - 70日龄时接受检查。产前暴露于乙醇的后代中脑缝际核中血清素能细胞数量显著减少。在旷场试验中，与对照组相比，它们在中央区域花费的时间更多。同样在高架十字迷宫试验中，产前暴露于乙醇的后代在开放臂上花费的时间比对照组更多。这些行为结果表明，产前暴露于乙醇的大鼠对焦虑不太敏感。然而，44%的产前暴露于乙醇的后代在高架十字迷宫的开放臂上表现出僵住行为，引发强烈焦虑，而完整对照组为0%，等热量蔗糖喂养对照组为12.5%。这些发现表明，产前乙醇暴露会降低焦虑的易感性和抗性。中缝核中血清素能神经元减少导致的血清素能作用不足可能导致了我们观察到的产前暴露于乙醇的大鼠中与焦虑相关行为的改变。
