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Acquisition, retention, or spontaneous recovery learning is impaired in mice by weekly treatments of 5‐fluorouracil or methotrexate
Author(s) -
Foley John J,
Raffa Robert B,
Walker Ellen A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.614
Subject(s) - spontaneous recovery , methotrexate , saline , extinction (optical mineralogy) , medicine , anesthesia , dipper , surgery , chemistry , ambulatory , mineralogy , ambulatory blood pressure
To assess the possible cognitive effects of repeated exposure to chemotherapeutic agents, the antimetabolites methotrexate (MTX) and 5‐fluorouracil (5‐FU) were administered to mice once weekly for three weeks, and then tested in a mouse model of learning and memory called autoshaping. Three groups of Swiss‐Webster mice (N=12 each) were injected i.p. with saline, 32 mg/kg MTX, or 75 mg/kg 5‐FU once a week for 21 days. Mice were presented a tone on a variable‐interval schedule, with the tone remaining on for 6 s, or until a nose‐poke response occurred to measure acquisition and retention (Day 22 and Day 23). After a center‐hole, nose‐poke during the tone, a dipper with Ensure solution was presented. If no response was made, the Ensure was automatically presented at the end of the 6 s period. The next two days, the Ensure solution was removed to measure extinction (Day 24) and spontaneous recovery (Day 25). 5‐FU treatment impaired acquisition on Day 22 and retention on Day 23 relative to saline controls. Repeated treatment of MTX did not alter acquisition or retention measures on Days 22 and 23; however, MTX produced longer session times and decreased rates of dipper responding on Day 25, suggesting an impairment of spontaneous recovery. These data demonstrate that repeated administration of chemotherapeutic agents to mice may produce deficits in learning, memory (5‐FU) or spontaneous recovery (MTX).