Brain neurotransmitter abnormalities and behavioral alterations induced by in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin at secondary sexual characteristic stage of development.

1. 我们观察到围产期暴露于2,3,7,8-四氯二苯并-对二恶英（TCDD）会导致皮肤上模拟软触的过度活跃运动反应增强。我们开发了一种新的研究仪器——触摸反应仪，用于计算实验动物的运动反应活动。用该仪器对社会孤立抑郁模型小鼠和二恶英暴露抑郁小鼠进行了实验。实验结果表明，该仪器可用于抑郁动物的筛选和抑郁程度的定量估计。雌性小鼠灌胃TCDD，与正常雄性小鼠交配。对其后代进行戳鼻试验，以评估围产期接触TCDD对第二性征和青春期发育阶段探索行为的影响。围生期暴露于TCDD的后代戳鼻子行为减少，表明TCDD暴露降低了这些阶段的探索行为。雌性妊娠小鼠口服TCDD，观察其后代在第二性征和青春期发育阶段的行为异常。雄性后代对皮肤上的机械软刺激表现出过度活跃的运动反应，如“踢开”、“逃跑”、“攻击”和“躲藏”。产后8 ~ 12周及以上均有上述行为。采用灌胃的方法对雌性孕鼠进行TCDD治疗，观察围生期TCDD暴露对其子代青春期和青年期蓝斑区活性的影响。高剂量TCDD暴露子代细胞核内可见少量免疫阳性的c-Fos神经元，而正常和低剂量子代细胞核内可见少量阳性细胞，提示围生期TCDD暴露对雄性子代蓝斑座活性无影响。

1. We observed that perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) caused enhanced hyperactive motor responses to soft touch simulation on the skin. We developed a new research instrument, Touch Response Meter, computing motor response activity of laboratory animals. The socially isolated depression model mice and the dioxin exposed depressed mice were tested in this instrument. We demonstrated that the screening of the depressed animals and quantitative estimating of degree of depression were computable using this new research instrument.2. Female ddY mice were administered TCDD by gavage and mated with normal male mice. The nose poke test was performed in their offspring to evaluate the effects of perinatal TCDD exposure on exploratory behavior at the secondary sexual characteristic and pubertal stages of development. The perinatal TCDD-exposed offspring at these stages showed decreased nose poke behavior, suggesting the perinatal TCDD exposure decrease exploratory behavior in these stages.3. Female pregnant mice were received oral administration of TCDD to evaluate the behavioral abnormalities of their offspring at the secondary sexual characteristic and pubertal stages of development. The male offspring showed hyperactive motor responses such as 'kicking off', 'escaping', 'attacking' and 'hiding' to mechanical soft stimulation on their skin. The behaviors continued from postnatal week 8 to 12 and more.4. Female pregnant mice were administered TCDD by gavage to evaluate the effect of perinatal TCDD exposure on the activity of the locus coeruleus of their offspring at the pubertal and young adult stages. A small number of immunopositive c-Fos neurons were observed in the nucleus in the high dosed TCDD-exposed offspring, but few positive cells were observed in the normal and low dosed offspring, indicating that the perinatal exposure of TCDD does not effect on the activity of the locus coeruleus of the male offspring at these stages.