Date of Completion

2018

Document Type

Honors College Thesis

Department

Neuroscience

Type of Thesis

Honors College

First Advisor

Eugene Delay

Second Advisor

Donna Toufexis

Third Advisor

Lawrence Rudiger

Keywords

Salt Taste, Chemotherapy, Psychophysics, Cell Renewal, Taste Transduction

Abstract

Chemotherapy is one of the most common treatments for cancer, however a side effect is often altered taste. This work examines how cyclophosphamide, a chemotherapy drug, affects salt taste in mice. Based on previous findings, we predicted that cyclophosphamide-induced disruptions in salt taste would be observed near days 2–4, 8– 2, and 22–24 days post treatment, and that multiple, smaller doses would cause more severe disruptions to taste. To test these predictions, we performed two experiments, one using brief-access testing to measure appetitive qualities, and another using operant conditioning to measure detection thresholds. After a single 100 mg/kg cyclophosphamide injection, peak alterations in brief-access lick rates were seen near days 5-8 and 15 post treatment, whereas peak alterations in detection thresholds were seen 6, 14 and 20 days post treatment. After five 20 mg/kg injections of cyclophosphamide, brief-access lick rates revealed disruptions only on post injection day 8 whereas thresholds appeared to cycle, gradually increased to and decreased from peak elevations on post treatment days 4, 10, 15, 20, and 23. While salt-taste functions were disrupted by cyclophosphamide, the patterns of these disruptions, and their severity, were less severe and shorter than expected from cell morphology studies, suggesting a functional compensation mechanism. Fractionation of cyclophosphamide dosing had minimum effect on brief access test but caused longer, cyclic-like disruptions of detection thresholds, compared to single-dose administration. This would suggest that dose fractionation can create a taste signal, which makes maintaining normal behavior harder in detection, but that does not alter acceptability. The differential effects of the fractionated cyclophosphamide treatment raise questions about what treatment provides the least impact on taste in cancer treatment, which could improve overall patient experience.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Available for download on Wednesday, May 03, 2152

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