Impact of chronic stressors on the anxiety profile of pregnant rats Soliani Flaviane Cristina de Brito Guzzo a , Cabbia Rafael a , Batistela Matheus Fitipaldi a , Almeida Amarylis Garcia a , Kümpel Vinícius Dias a , Yamauchi Junior Luiz a , Frei Fernando b , Andrade Telma Gonçalves Carneiro Spera de a, ⁎ a UNESP — Univ Estadual Paulista, FCL, Department of Biological Science, Laboratory of Physiology, Avenida Dom Antônio 2100, 19806-900, Assis, SP, Brazil b UNESP — Univ Estadual Paulista, FCL, Department of Biological Science, Laboratory of Statistic, Avenida Dom Antônio 2100, 19806-900, Assis, SP, Brazil HIGHLIGHTS • The manifestation of anxiety in pregnant rats is greater at the end of gestation. • Social separation causes anxiolysis in the third gestational week. • Unpredictable chronic stress increases anxiety, especially at the end of 2nd week. abstract article info Article history: Received 25 November 2014 Received in revised form 19 January 2015 Accepted 3 February 2015 Available online 7 February 2015 Keywords: Anxiety Pregnancy Social separation Unpredictable chronic stress The manifestation of anxiety during pregnancy can be caused by multiple factors and may have emotional and physical consequences for both the mother and the fetus. The prevalence of gestational anxiety has grown in recent years, making the development of studies for its comprehension essential. Thus, the aim of this investiga- tion was to evaluate the effects of predictable and unpredictable chronic stressors on the anxiety profile of rats in three distinct stages of pregnancy (1st, 2nd and 3rd weeks). Wistar dams were divided into three groups: control, social separation and unpredictable chronic stress. Behavioral assessments were conducted in the Elevated Plus- Maze at the end of the 1st, 2nd and 3rd weeks of gestation. The results showed that there was increased anxiety in the proximity of parturition in control dams. Chronic stressors differentially affected the behavior of pregnant rats according to the gestational period where they were applied: social separation decreased anxiety at the end of the 3rd week, while unpredictable chronic stress caused increased anxiety, especially at the end of the 2nd gestational week. These results show that there is a critical time during pregnancy for the onset of anxiety in control rats, depending on the gestational stage. The exposure to different types of chronic stressors may result in distinct behaviors related to this disorder. © 2015 Elsevier Inc. All rights reserved. 1. Introduction Mental disorders afflict approximately 450 million people world- wide [1]. Among them, anxiety has a lifetime prevalence of 31.2% in the general population: 36.4% for women and 25.4% for men [2]. Conse- quently, there has been an alarming increase in the consumption of drugs used for treatment of this disorder [3]. It is known that women are more susceptible to the development and manifestation of different types of anxiety, especially in developmental periods (puberty and climacteric), during the female hormonal cycle (premenstrual period) or as a result of bilateral ovariectomy, i.e., conditions where estrogen and progesterone concentrations are at low or unstable levels [4–10]. Besides, pregnancy is also a critical period for the manifestation of this disturbance. The prevalence of anxiety disorders during pregnancy varies according to the evaluated period, in addition to factors like socioeconomic status, ethnicity, age, personal resources (self-esteem, optimism and self-control), relationship and social support, previous de- liveries, and medical risks, among others (see [11], for review). A study conducted by Lee and colleagues [12] showed that 54% of women report- ed anxiety in pregnancy for at least one trimester. Pregnancy is a time of crisis, characterized by profound changes in social, professional, and emotional life and the body of a woman. More- over, it is well-known that modern women, in addition to incubating the conceptus throughout the gestational period, delivering and breast- feeding their children, play other social roles, as wife, mother, and profes- sional, among numerous other functions they perform. This set of func- tions, added to the anatomical, physiological and psychological changes inherent in pregnancy can enhance the impact of stressors, impairing life quality. All this stress may also result in drastic consequences for the mother's body, such as suppression of the immune response [13], changes in eating habits [14] and in sleep pattern [15], predisposing her even more Physiology & Behavior 142 (2015) 137–145 ⁎ Corresponding author. E-mail address: raica@assis.unesp.br (A. Telma Gonçalves Carneiro Spera de). http://dx.doi.org/10.1016/j.physbeh.2015.02.014 0031-9384/© 2015 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Physiology & Behavior journal homepage: www.elsevier.com/locate/phb