| Title: | Effects of in utero exposure to fluoxetine on the gastrointestinal tract of rat offspring |
| Author(s): | Prowse KL; Law H; Raez-Villanueva S; Markovic F; Wang M; Borojevic R; Parsons SP; Vincent AD; Holloway AC; Ratcliffe EM; |
| Address: | "Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada. ROR: https://ror.org/02fa3aq29 Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada. ROR: https://ror.org/02fa3aq29 Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada. ROR: https://ror.org/02fa3aq29 Medicine, McMaster University, Toronto, Ontario, Canada. ROR: https://ror.org/02fa3aq29 Pediatrics, McMaster University, Hamilton, Ontario, Canada. ROR: https://ror.org/02fa3aq29" |
| Journal Title: | Am J Physiol Gastrointest Liver Physiol |
| ISSN/ISBN: | 1522-1547 (Electronic) 0193-1857 (Linking) |
| Abstract: | "Perinatal exposure to selective serotonin reuptake inhibitors (SSRIs) has been shown to disrupt the development of serotonergic signaling pathways. Serotonin (5-hydroxytryptamine; 5-HT) signaling is critical for gastrointestinal homeostasis; changes in 5-HT expression and regulation have been associated with gastrointestinal diseases of motility and inflammation. We tested the hypothesis that perinatal exposure to the SSRI, fluoxetine, can influence the development of the gastrointestinal tract in exposed offspring. Female nulliparous Wistar rats were given fluoxetine (10 mg/kg) or vehicle control from 2 weeks prior to mating until weaning; small and large intestine of female and male offspring were collected at postnatal days 1, 21 (P1, P21) and 6 months of age. In histological preparations, the proportion of serotonergic neurons was significantly increased in the colons of both female and male fluoxetine-exposed compared to control offspring at P21 (peak exposure). At 6 months of age, male fluoxetine-exposed offspring had a significant increase in circulating 5-HT, with a significant decrease in transcripts encoding the 5-HT(2A) receptor and monoamine oxidase as compared to control offspring. Measurement of spatiotemporal mapping of intestinal contractile activity at 6 months of age revealed a significant increase in frequency of colonic contractions in female fluoxetine-exposed compared to control animals. In utero exposure to fluoxetine was not found to increase susceptibility to dextran sulfate sodium-induced acute colitis at 6 months. These findings suggest that fluoxetine-exposure during development can lead to changes in serotonergic neurons at the peak of exposure with sex-specific changes in 5-HT signaling and colonic motility in adulthood" |
| Keywords: | enteric nervous system fluoxetine gastrointestinal tract perinatal serotonin; |
| Notes: | "PublisherProwse, Katherine L Law, Harriett Raez-Villanueva, Sergio Markovic, Filip Wang, Megan Borojevic, Rajka Parsons, Sean P Vincent, Alexander D Holloway, Alison C Ratcliffe, Elyanne M eng 350785/Crohn's and Colitis Foundation (CCF)/ 2023/09/19 Am J Physiol Gastrointest Liver Physiol. 2023 Sep 19. doi: 10.1152/ajpgi.00223.2022" |
