Prenatal psychological stress causes higher emotionality, depression-like behavior, and elevated activity in the hypothalamo-pituitary-adrenal axis
Introduction
In humans, it has been reported that stressful events during pregnancy may raise the risk of psychiatric disorders in offspring (Wadhwa et al., 2001, Weinstock, 2001, Maccari et al., 2003). Studies with rodents give us a clearer relationship between stressful treatment during pregnancy and changes in the physiology and behavior of the offspring (Kofman, 2002, Maccari et al., 2003, Weinstock, 2005). Generally, prenatally stressed rats showed higher emotional reactivity, higher levels of anxiety, and depression-like behavior. In such studies, physical stress was given to the dams. For example, restraint stress, to which dams were exposed for 45 min three times per day with bright light during the last trimester of gestation, has been most widely used in recent studies with rodents (Bhatnagar et al., 2005, Viltart et al., 2006, Wang et al., 2006). Additionally, foot shock (Estanislau and Morato, 2005), injection of saline (White and Birkle, 2001), loud noise (Wakshlak and Weinstock, 1990), or a combination of these (Koenig et al., 2005) were used as physical stress. However, in humans, we may say that pregnant women are exposed to psychological stress more frequently than to physical stress. Although pregnant women may experience physical injury caused by accidents or infections, they are more often exposed to psychological stress, such as anxiety about their babies and their entirely new lifestyle, financial problems, workplace worries, and so on. Therefore, to examine the etiology of psychiatric disorders caused by prenatal stress in humans, one should use an animal model, in which the effects induced by psychological stress but not physical stress can be evaluated. However, as stated above, to our knowledge, physical stress was given to the dams in almost all studies with rodents. In fact, Chapillon et al. (2002) reviewed a series of their studies with emotional stress. In their experiment, where they exposed dams to a cat as a prenatal stress, exposure to a cat was acutely carried out at gestational days 10, 14, or 19. On the other hand, we intended to expose dams to psychological stress during the last trimester of gestation to compare directly the effect of conventional restrain stress procedure (Bhatnagar et al., 2005, Viltart et al., 2006, Wang et al., 2006). Furthermore, according to their description (Lordi et al., 1997), when dams were put in a box with a cat together, “rats exhibited strong motor and autonomic reactions”. This suggested that dams and fetus would have considerable physical stress as well as psychological stress. Moreover, intensity of stress would be difficult to control because a cat put in a box would not behave against each pregnant rat in a similar manner. Therefore, in this study, we used psychological stress produced by the social communication box (Ogawa and Kuwabara, 1966). The communication box is an apparatus in which subjects observe a rat being electrically shocked behind a transparent wall. This seems to expose subjects to psychological stress with no physical stress. To examine emotional reactivity, depression-like behavior, and learning ability of male offspring from the dams exposed to psychological stress, comparing with offspring from untreated dams, rats were tested in an open field test, a forced swim test, and a context conditioning. Additionally, neurobiological differences were examined by measuring plasma corticosterone contents and the number of Fos immunopositive cells in some brain regions between them.
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Animals
Six Sprague–Dawley pregnant rats (9-week-old) at the 13th gestational day and six Sprague–Dawley female rats (10-week-old) were obtained from Charles-River, Japan, and were individually housed on a 12 h light/dark cycle (light on: 08:00 h) with free access to food and water. The pregnant rats were nulliparous until this pregnancy. The pregnancy was confirmed by the existence of the plug in the vaginas. Three pregnant females were given psychological stress and the others were not. Six nonpregnant
Body weights of dams and offspring
Body weights of dams during stress exposure were analyzed. On the initial day, mean body weights ± standard error of dams exposed to stress and dams not exposed to stress were 305.8 ± 15.6 and 309.1 ± 14.8, respectively. On the last day for the stress exposure, they were 349.8 ± 16.2 and 358.0 ± 17.9, respectively. That is, gains of body weights of dams exposed to psychological stress were slightly lower than dams without stress exposure. However, the differences were not significant.
Body weights of
Discussion
In the present study, we demonstrated that psychological stress given to pregnant dams could cause enhanced emotionality, depression-like behavior, and enhanced activity in the hypothalamo–pituitary–adrenal (HPA) system of offspring in rats.
In this study, the dams delivering C groups were not placed in the novel communication box, while the dams delivering PSY groups were placed in such a box. Therefore, exposure to the novel environment, in addition to the exposure to shocked rats, may produce
Acknowledgement
We thank Miss Fumiko Tsuda for her technical assistance with this work.
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