Figure 2.

Citalopram normalizes the effects of prenatal stress on dam behavior and tissue serotonin levels in fetal forebrain and frontal cortex. (A) Timed-pregnant mice were subjected to a sequence of CUS from E8 to E17 (details in Table S1). Dams in the CIT and CUS+CIT group received CIT through drinking water from E8 to E17. Only dams in the CUS and CUS+CIT groups were exposed to stressors. Mice were tested in the OFT on E15 followed by the FST on E16. (B) Immobility times in the FST were significantly greater in CUS-exposed dams compared to the other study groups. This effect was reversed by exposure to CIT during gestational CUS (CUS+CIT group). Immobility times in the untreated control and CIT groups were not significantly different. (C) The CUS paradigm induced a significant decrease in time spent in the center of the OFT when compared to untreated controls. This effect was reversed in the CUS+CIT group. (D) There were no differences in total distance traveled in the OFT between groups. (B–D) N = 7–9 dams per condition. (E) Representative activity traces acquired during OFT sessions. The blue squares denote the boundary of the center area quantified in panel B. (F) Serotonin and 5-HIAA levels were quantified in the fetal forebrain (FB), hindbrain (HB), and frontal cortex (FC, dotted line) at E17 by HPLC (N = 7–9 dams per condition, 3 fetal fore/hindbrain samples per dam). (G, H) A significant increase in forebrain (G) and frontal cortex (H) serotonin tissue levels was observed following maternal CUS, whereas CIT alone induced a significant decrease compared to untreated controls at E17. Forebrain serotonin levels following exposure to CUS and CIT (CUS+CIT group) were not different from untreated controls in both regions. Data are means ± SEMs. *P < 0.05, **P < 0.01, or ***P < 0.001.