Cyclophosphamide-induced disruptions to appetitive qualities and detection thresholds of NaCl: Comparison of single-dose and dose fractionation effects

Abstract

Chemotherapy is one of the most common treatments for cancer; however, a side effect is often altered taste. This study examined how cyclophosphamide, a chemotherapy drug, affects salt taste in mice. On the basis of previous findings, it was predicted that cyclophosphamide-induced disruptions in salt taste would be observed near days 2-4, 8-12, and 22-24 posttreatment, and that multiple, smaller doses would cause more severe disruptions to taste. To test these predictions, two experiments were performed, 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 posttreatment, whereas peak alterations in detection thresholds were seen days 6, 14, and 20 posttreatment. After five 20 mg/ kg injections of cyclophosphamide, brief access lick rates revealed disruptions only on postinjection day 8 whereas thresholds appeared to cycle, gradually increased to and decreased from peak elevations on posttreatment days 4, 10, 15, 20, and 23. Although salt taste functions were disrupted by cyclophosphamide, the patterns of these disruptions were less severe and shorter than expected from cell morphology studies, suggesting a functional adjustment to maintain behavioral accuracy. Fractionation of cyclophosphamide dosing had minimum effect on brief access responses but caused longer, cyclic-like disruptions of detection thresholds compared to single-dose administration.