A8 INFLUENCE OF MATERNAL SSRI EXPOSURE ON THE DEVELOPMENT OF THE ENTERIC NERVOUS SYSTEM

Antidepressants, including selective serotonin reuptake inhibitors (SSRIs) are commonly used during pregnancy. Approximately 7% of women in North America require SSRI in the perinatal period. Perinatal exposure to SSRIs has been shown to disrupt the development of serotonergic signaling pathways in the brain. However, the potential for changes to the enteric nervous system (ENS) over a period of postnatal development has not been explored. To test the hypothesis that perinatal exposure to SSRIs can influence the development of the ENS. Female Wistar rats were given fluoxetine (10mg/kg/d) or vehicle (cookie dough) from 2 weeks prior to mating until weaning (postnatal day [P] 21). Offspring were collected from SSRI-treated and control rats on P1, P21 and P6 months to see if changes were persistent. Enteric neurons in the myenteric plexus were visualized in whole mount preparations of jejunum, ileum and colon. Total number (#) of enteric neurons (EN) and serotonergic neurons (SN) were visualized with immunostaining using antibodies to HuC/D and 5-HT, respectively. Percentage of SSRI-expressing enteric neurons were calculated as a percentage of total neurons using image analysis software (Velocity). Female (F) and male (M) offspring were analyzed separately. On P1, no significant differences were found in the total # of EN nor in SN between SSRI-exposed and control offspring in the jejunum, ileum and M colon (n=6–10). However, a significant decrease between the total # of EN and SN was found in the SSRI-exposed F offspring colon (13.6% vs 9.3%; p=0.04; n=6–9). On P21, no significant differences were found in the total # of EN in the ileum and colon of SSRI-exposed and control offsprings. There was also no significant difference found between the percentage of SN between the SSRI-exposed and control ileum (n=6–10). Significant differences were found in the percentage of SN in both F (1.4% vs 7.6%; p=0.009); n=5–6) and M colons (1.7% vs 6.9%; p=0.002; n=5–8). At 6 months of age, there was no significant difference in the percentage of total # of EN nor in SN between SSRI-exposed and control offspring. Our results suggest that SSRI exposure in the in utero and perinatal period play a role in serotonergic signaling pathways involved in the development of the enteric nervous system of the developing offspring. However, these changes improve over time, which may be attributed to the plasticity of the ENS. CCFA Broad Foundation