Department of Cognitive Behavioral Physiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670, Japan.
Prog Neuropsychopharmacol Biol Psychiatry. 2012 Dec 3;39(2):273-9. doi: 10.1016/j.pnpbp.2012.06.016. Epub 2012 Jul 1.
Bisphenol A (BPA), an endocrine-disrupting chemical, is widely present in the environment. It has been reported that perinatal exposure to low doses of BPA that are less than the tolerable daily intake level (50μg/kg/day) affects anxiety-like behavior and dopamine levels in the brain. Although the dopaminergic system in the brain is considered to be related to anxiety, no study has reported the effects of low-dose BPA exposure on the dopaminergic system in the brain and on anxiety-like behavior using the same methods of BPA exposure. To investigate the relationship between alterations in anxiety-like behavior and changes in the dopaminergic system in the brain induced by BPA, we examined the effects of BPA on anxiety-like behavior using an open field test in juvenile and adult mice and measured DA and DOPAC levels and the DOPAC/DA ratio in the dorsal hippocampus (HIP), amygdala (AMY), and medulla oblongata (MED) using high-performance liquid chromatography (HPLC) in adult mice. In males, BPA decreased the time spent in the center area of the open field in both juveniles and adults. In addition, BPA increased DA levels in the dorsal HIP and MED and decreased the DOPAC/DA ratio in the dorsal HIP, AMY, and MED in adults. The activity of monoamine oxidase (MAO)-B, the enzyme that metabolizes DA into DOPAC, was reduced in the MED. In females, those changes were not observed. These results suggest that an increase in anxiety-like behavior induced by perinatal exposure to BPA may be related to decreases in DA metabolites in the brain, and there are sex differences in those BPA effects.
双酚 A（BPA）是一种内分泌干扰化学物质，广泛存在于环境中。有报道称，围产期接触低于可耐受日摄入量（50μg/kg/天）的低剂量 BPA 会影响大脑中的焦虑样行为和多巴胺水平。尽管大脑中的多巴胺能系统被认为与焦虑有关，但没有研究报告低剂量 BPA 暴露对大脑中多巴胺能系统和焦虑样行为的影响使用相同的 BPA 暴露方法。为了研究 BPA 引起的焦虑样行为改变与大脑多巴胺能系统改变之间的关系，我们使用开放式场测试检查了 BPA 对幼年和成年小鼠焦虑样行为的影响，并使用高效液相色谱法（HPLC）测量了成年小鼠背侧海马体（HIP）、杏仁核（AMY）和延髓（MED）中的 DA 和 DOPAC 水平以及 DOPAC/DA 比值。在雄性小鼠中，BPA 减少了幼年和成年小鼠在开放式场中心区域的停留时间。此外，BPA 增加了背侧 HIP 和 MED 中的 DA 水平，降低了背侧 HIP、AMY 和 MED 中的 DOPAC/DA 比值。单胺氧化酶（MAO）-B 的活性，即将 DA 代谢为 DOPAC 的酶，在 MED 中降低。在雌性小鼠中，没有观察到这些变化。这些结果表明，围产期接触 BPA 引起的焦虑样行为增加可能与大脑中 DA 代谢物的减少有关，并且这些 BPA 效应存在性别差异。
