Perinatal fluoxetine dose-dependently affects prenatal stress-induced neurobehavioural abnormalities, HPA-axis functioning and underlying brain alterations in rat dams and their offspring

Both untreated and SSRI antidepressant treated maternal depression during the perinatal period can pose both short-and long-term health risks to the offspring. Therefore, it is essential to have an effective SSRI treatment consisting of the lowest effective dose beneficial to the mother, without causing adverse effects on offspring development. The effects of prenatal stress on neurobehavioral outcomes were studied in the pregnant and lactating rat dam, and her offspring. Furthermore, stressed dams were treated with different doses of fluoxetine (FLX; 5, 10and 25 mg/kg) during pregnancy and the postpartum period. We found that prenatal stress-induced anxiety-and depressive-like behaviour and increased HPA-axis function in pregnant and postpartum dams, and in offspring. Maternal stress impaired object recognition but did not affect spatial memory in offspring. Prenatal stress decreased whole-brain serotonin and brain-derived-neurotrophic-factor, and increased interleukin-17 and malondialdehyde, but did not affect oxytocin and interleukin-6 in the brains of offspring. Maternal treatment with 5 mg/kg FLX during the perinatal period did not rescue any stress-induced anxiety/depressive-like behaviour in the pregnant and postpartum dam and had only a few rescuing effects in offspring. Maternal FLX treatment with 10 mg/kg did rescue most stress-induced anxiety-and depressive-like behaviour or HPA-axisfunction in dams and offspring. The highest dose tested, 25 mg/kg FLX, had the rescuing properties in dams while having the same, or an even greater, detrimental effect as prenatal stress on offspring behaviour and molecular alterations in the brain. Our results show prenatal stress rescuing properties for FLX treatment in the pregnant and postpartum dam, with dose-dependent effects on the offspring.

Automated summary

Our study found that prenatal stress induced anxiety and depressive behaviors in pregnant and postpartum dams, and in offspring, as well as affecting HPA-axis function. Maternal stress impaired object recognition but did not affect spatial memory in offspring. Prenatal stress decreased whole-brain serotonin and brain-derived neurotrophic factor, and increased interleukin-17 and malondialdehyde, but did not affect oxytocin and interleukin-6 in the brains of offspring.