Esketamine ameliorates prenatal stress-induced postpartum depression and sex-related behavioral differences in adolescent progeny

Abstract

Background

Prenatal stress leads to postpartum depression and is associated with developmental issues in offspring. Esketamine quickly and effectively prevents or treats postpartum depression. However, the long-term effects of esketamine on progeny development are unknown.

Methods

CRS during pregnancy was used to establish the postpartum depression animal model. After confirming pregnancy, all mice were randomly divided into three groups: pregnant control group, pregnant restraint group, and pregnant restraint + esketamine group. Mice in the restraint + esketamine group received esketamine intraperitoneal injection on postpartum days 1–5. Behavioral tests were performed on maternal mice five days after delivery. Another cohort of mice was used to test the effects of esketamine on the behavior of offspring mice. The levels of ACTH and CORT were measured in offspring mice in response to acute restraint stress by ELISA.

Results

We found that prenatal CRS induced postpartum depression-like behaviors in maternal mice and sex-related differential behaviors in adolescent offspring. Female offspring exhibited depression-like behaviors, and male offspring showed memory deficits. Esketamine improved postpartum depression-like behaviors in maternal mice and behavioral changes in teenage offspring. Prenatal CRS led to hyperresponsiveness of ACTH and CORT to acute restraint stress in adolescent offspring. Compared with the offspring in the control group, the restraint group increased secretion of ACTH and CORT during acute restraint stress.

Conclusion

Prenatal CRS led to postpartum depression-like behaviors in maternal mice and sex-related differential behaviors in adolescent offspring. Esketamine effectively improves postpartum depression-like behaviors in maternal mice and behavioral changes in adolescent offspring.