Disrupted serotonin system development via early life antidepressant exposure impairs maternal care and increases serotonin receptor expression in adult female offspring

Dev Psychobiol. 2022 Sep;64(6):e22292. doi: 10.1002/dev.22292.

Abstract

Manipulating serotonin (5-HT) levels in the developing brain elicits a range of effects on brain function and behavior. For example, early-life exposure to selective 5-HT reuptake inhibitor (SSRI) antidepressants disrupts dorsal raphe function and triggers aberrant adult behaviors such as increased passive stress coping and anhedonia. However, much less is understood about how alterations in 5-HT signaling in early life impact outcomes in female offspring, including critical social functions such as maternal care. The present study shows that early-life SSRI exposure disrupts adult female offspring's maternal behavior. Pregnant/postpartum female Sprague-Dawley rats were treated with the SSRI citalopram in drinking water or provided regular tap water as control. Female offspring were raised to adulthood and mated with treatment-naïve males. Following parturition, we observed maternal behavior during portions of the light and dark phases of postnatal days (P)1-14. Relative to controls, dams with a history of early-life SSRI exposure exhibited decreased maternal care, including diminished arched-back nursing, reduced licking and grooming of pups, and increased behavioral inconsistency. Brains were collected from dams with and without a history of early-life SSRI exposure to measure relative mRNA expression of select 5-HT receptor transcripts (5HTR1A, -1B, -2A, -2C) in regions involved in maternal care. Early-life SSRI exposure augmented expression of 5-HTR1A in the medial preoptic area and 5-HTR1B, 5-HTR2A, and 5-HTR2C in the prefrontal cortex. These results demonstrate that early alterations to 5-HT signaling through SSRI exposure may disrupt nurturing parental behaviors and 5-HT receptor expression in affected female rat offspring.

Keywords: development; maternal care; serotonin; serotonin receptors.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antidepressive Agents
  • Female
  • Male
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin* / metabolism

Substances

  • Antidepressive Agents
  • Receptors, Serotonin
  • Serotonin Uptake Inhibitors
  • Serotonin