Date of Award

January 2018

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Robert A. Cowles

Abstract

Parenterally-administered selective serotonin reuptake inhibitors (SSRI), such as citalopram, increase intestinal mucosal absorptive surface by day 7 of treatment. We hypothesized that enteral citalopram would also induce intestinal mucosal growth, thus allowing for therapy with an oral agent. In the study’s first phase, C57BL/6 mice received peanut butter (PB) pellets containing 10, 50, or 100 mg/kg/day citalopram for 7 days; or 25 mg/kg/day citalopram for 14 or 21 days; or plain PB pellets for 7, 14, or 21 days. In the second phase, C57BL/6 mice received 0, 10, 25, or 50 mg/kg/day citalopram in drinking water for 2, 3, 6, or 8 weeks, or for 6 weeks followed by 2 weeks of drug withdrawal. Two-centimeter ileal segments were harvested and prepared for microscopic assessment of villus height (VH), crypt depth (CD), villus width (VW), and crypt width (CW). Mucosal surface area (MSA) was calculated and data were compared using Student’s t-test. Enteral citalopram given for 14 days in PB pellets resulted in an increased VH (p <0.0001), VW (p = 0.0058), and ileal MSA per mm2 (p = 0.0007). The increase in MSA was sustained at 21 days (p <0.0001). When citalopram was given in drinking water, VH was greater than controls by week 3 (p <0.0001 across all three doses); however, MSA per square millimeter was not significantly increased, regardless of treatment dose or duration. Further work is needed, but SSRIs show some promise in the short-term period as oral therapy for serious intestinal disorders such as short bowel syndrome.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 06/27/2020

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