Effects of < em > in utero < /em > exposure to fluoxetine on the gastrointestinal tract of rat offspring

Am J Physiol Gastrointest Liver Physiol. 2023 Sep 19. doi: 10.1152/ajpgi.00223.2022. Online ahead of print.ABSTRACTPerinatal 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-HT2A 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 fl...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Source Type: research