Most pregnant women are at risk of showing some emotional abnormality, since some biological functions such as hormonal systems may dramatically change in pregnancy. Some of them may be exposed to strong stress as hesitation of positive drug therapies because of worries regarding adverse effects on the embryo. A growing body of evidence suggests that prenatal stress increases the vulnerability to neuropsychiatric disorders, including depression and anxiety. However, the mechanisms involved are still unknown. To clarify the influence of exposure to prenatal stress on emotional development, we examined behavioral responses in offspring exposed to weak- or strong-prenatal restraint stress. We found that offspring that had been exposed to strong stress displayed anxiety-like behavior as determined by the elevated plus-maze test. It has been widely accepted that central serotonin (5-hydroxytryptamine; 5-HT) neurons play a critical role in emotional behaviors. Immunohistochemical studies showed that exposure to strong-prenatal restraint stress increased the expression of 5-HT-positive cells in the dorsal raphe nuclei in mice. Moreover, under these conditions, tryptophan hydroxylase-like immunoreactivities were also dramatically increased. In contrast, these behavioral and neurochemical abnormalities were not observed in offspring that had been exposed to weak-prenatal restraint stress. These findings indicate that exposure to excessive prenatal stress induces anxiety-like behavior together with disruption of the development of 5-HT neurons in mice.
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