Brain neurotransmitter abnormalities and behavioral alterations induced by in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

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1. Female ddY mice were administered 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by gavage and mated with normal male mice. Their male offspring were used to evaluate the effects of in utero and lactational TCDD- exposure on onset of depression induced by protracted stress at the secondary sexual characteristic, pubertal and young adult stages of development. The offspring were weaned at postnatal 21 day and socially isolated over four weeks to be taken depression. The brain concentration of noradrenaline in these stages of offspring was decreased and the social behaviors were despaired compared to those of the socially isolated TCDD- unexposed control mice at the same stages. The results indicate that the perinatal exposure of TCDD has effects on the mechanism of onset of depression in these stages of development in the male offspring.2. Female pregnant ddY 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. When the offspring were received mechanical soft touch stimulations on their skin, the offspring showed hyperactive responses such as kicking-off, escaping, attacking and hiding behaviors. The normal control mice did not show these abnormal behaviors. On the other hand, the socially isolated depressed mice showed the same hyperactive responses to the soft touch stimulations. It has been known that the brain monoamine changes are partly common in depressed patients, depression model animals such as socially isolated mice and the perinatally dioxin-exposed animals. It was considered that the behavioral abnormalities observed at the TCDD-exposed mice at the secondary sexual characteristic and pubertal stages of development were a kind of depression symptoms, indicating that the perinatal exposure of TCDD is one of the risk factors of the onset of depression in these stages of development.