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.

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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.