Effects of repeated administration of chemotherapeutic agents tamoxifen, methotrexate, and 5-fluorouracil on the acquisition and retention of a learned response in mice.
Effects of repeated administration of chemotherapeutic agents tamoxifen, methotrexate, and 5-fluorouracil on the acquisition and retention of a learned response in mice.
复制标题
DOI：
10.1007/s00213-011-2310-8
复制
发表时间：
2011-10
影响因子：
3.4
通讯作者：
Raffa, Robert B.
中科院分区：
文献类型：
--
作者：
Walker, Ellen A.;Foley, John J.;Clark-Vetri, Rachel;Raffa, Robert B.
许多癌症化疗药物与乳腺癌患者的记忆丧失有关，尽管这种影响的因果关系知之甚少。为了评估反复暴露于化疗药物的潜在认知影响，我们给小鼠单独和联合使用选择性雌激素受体调节剂他莫昔芬或抗代谢化疗药物甲氨蝶呤和5-氟尿嘧啶，并在学习和记忆试验中对其进行测试。Swiss-Webster雄性小鼠每周一次注射生理盐水、32 mg/kg他莫昔芬、3.2或32 mg/kg甲氨蝶呤、75 mg/kg 5-氟尿嘧啶、3.2或32 mg/kg甲氨蝶呤与75 mg/kg 5-氟尿嘧啶的组合，持续3周。在第23天和第24天，测试小鼠在称为自动成形的学习过程中获得和保持鼻子戳反应。此外，他莫昔芬的急性效应在其他小鼠中以类似的程序进行评估。在4周的过程中，相对于盐水治疗，单独和组合的化疗剂减轻了体重。重复治疗与他莫昔芬产生收购和保留效果相对于盐水治疗组，虽然急性他莫昔芬是没有效果，除了在行为毒性剂量。甲氨蝶呤与5-氟尿嘧啶联合重复治疗对尿潴留产生影响，但这些变化的幅度取决于甲氨蝶呤的剂量。这些数据表明，他莫昔芬或甲氨蝶呤和5-氟尿嘧啶的某些组合的重复给药可能会产生的收购或保留的学习反应，这表明潜在的预防或补救策略可能会考虑在脆弱的患者群体的缺陷。
A number of cancer chemotherapeutic agents have been associated with a loss of memory in breast cancer patients although little is known of the causality of this effect. To assess the potential cognitive effects of repeated exposure to chemotherapeutic agents, we administered the selective estrogen receptor modulator tamoxifen or the antimetabolite chemotherapy, methotrexate, and 5-fluorouracil, alone and in combination to mice and tested them in a learning and memory assay. Swiss-Webster male mice were injected with saline, 32 mg/kg tamoxifen, 3.2 or 32 mg/kg methotrexate, 75 mg/kg 5-fluorouracil, 3.2 or 32 mg/kg methotrexate in combination with 75 mg/kg 5-fluorouracil once per week for 3 weeks. On days 23 and 24, mice were tested for acquisition and retention of a nose-poke response in a learning procedure called autoshaping. In addition, the acute effects of tamoxifen were assessed in additional mice in a similar procedure. The chemotherapeutic agents alone and in combination reduced body weight relative to saline treatment over the course of 4 weeks. Repeated treatment with tamoxifen produced both acquisition and retention effects relative to the saline-treated group although acute tamoxifen was without effect except at a behaviorally toxic dose. Repeated treatment with methotrexate in combination with 5-fluorouracil produced effects on retention, but the magnitude of these changes depended on the methotrexate dose. These data demonstrate that repeated administration of tamoxifen or certain combination of methotrexate and 5-fluorouracil may produce deficits in the acquisition or retention of learned responses which suggest potential strategies for prevention or remediation might be considered in vulnerable patient populations.
登录
查看更多内容
影响因子：
4.5
作者：
Jenkins, VA;Bloomfield, DJ;Edginton, TL
通讯作者：
Edginton, TL
影响因子：
2.4
作者：
Janelsins, Michelle C.;Roscoe, Joseph A.;Gross, Robert A.
通讯作者：
Gross, Robert A.
影响因子：
3.3
作者：
Gandal, M. J.;Ehrlichman, R. S.;Siegel, S. J.
通讯作者：
Siegel, S. J.
影响因子：
11.5
作者：
Lee, GD;Longo, DL;Ingram, DK
通讯作者：
Ingram, DK
影响因子：
--
作者：
Bonadonna, G;Moliterni, A;Valagussa, P
通讯作者：
Valagussa, P