Effects of chemotherapy on operant responding for palatable food in male and female mice.
Effects of chemotherapy on operant responding for palatable food in male and female mice.
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DOI：
10.1097/fbp.0000000000000635
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发表时间：
2021-08-01
影响因子：
1.6
通讯作者：
Damaj MI
中科院分区：
文献类型：
--
作者：
Meade JA;Fowlkes AN;Wood MJ;Kurtz MC;May MM;Toma WB;Warncke UO;Mann J;Mustafa M;Lichtman AH;Damaj MI
接受癌症化疗药物治疗的患者常报告出现化疗诱导的周围神经病变（CIPN）、情绪变化（抑郁、焦虑）以及功能受损。CIPN的啮齿动物模型仅引发有限的功能行为改变，这给开发化疗诱导行为性抑郁的临床前模型带来了挑战。
本研究考察了化疗诱导的机械性痛觉过敏（紫杉醇：累积剂量32毫克/千克或64毫克/千克；奥沙利铂：累积剂量30毫克/千克）对行为性抑郁的影响，通过在食物限制期和随意进食期对美味食物的操作性反应、在随意进食普通饲料时对非条件可得美味食物的消耗以及自愿转轮运动来衡量。这些研究采用了两种近交系小鼠品系（C57BL/6J和Balb/cJ），还考察了潜在的性别差异。
在各项研究的观察期内（至少1个月，最长7个月），所有化疗方案均导致了严重的机械性痛觉过敏，但没有一种治疗改变了自愿转轮运动或非条件美味食物的消耗。高剂量的紫杉醇暂时降低了处于食物限制期或随意进食普通饲料的雄性C57BL/6J小鼠对美味食物的操作性反应。然而，紫杉醇并未降低自由进食的雌性C57BL/6J小鼠或任一性别的Balb/cJ小鼠对美味食物的操作性反应。此外，奥沙利铂对随意进食普通饲料的雄性或雌性C57BL/6J小鼠对美味食物的操作性反应没有显著影响。
这些研究结果表明，在所测试的实验中，化疗诱导的机械性痛觉过敏与行为性抑郁之间存在分离。紫杉醇对雄性C57BL/6J小鼠操作性反应的短暂影响，可能代表了该品系中与化疗相关的疼痛样行为的一种短暂行为关联。
Patients treated with cancer chemotherapeutics frequently report chemotherapy-induced peripheral neuropathy (CIPN), changes in mood (depression, anxiety), and functional impairments. Rodent models of CIPN elicit limited alterations in functional behaviors, which pose challenges in developing preclinical models of chemotherapy-induced behavioral depression. The present study examined the consequences of chemotherapy-induced mechanical hypersensitivity (paclitaxel: 32 mg/kg or 64 mg/kg, cumulative; oxaliplatin: 30 mg/kg, cumulative) on behavioral depression, as measured with operant responding for palatable food during periods of food restriction and ad libitum chow, consumption of non-contingently available palatable food in the presence of ad libitum chow, and voluntary wheel running. These studies employed two inbred mouse strains (C57BL/6J and Balb/cJ) and also examined potential sex differences. All chemotherapeutic regimens caused profound mechanical hypersensitivity for the duration of the observation periods of the various studies (a minimum of 1 month, and up to 7 months), but none of the treatments changed voluntary wheel running or consumption of non-contingent palatable food. The high dose of paclitaxel temporarily reduced operant responding for palatable food in male C57BL/6J mice undergoing food restriction or maintained on ad libitum chow. However, paclitaxel failed to decrease operant responding for palatable food in free-feeding female C57BL/6J mice or Balb/cJ mice of either sex. Moreover, oxaliplatin did not significantly alter operant responding for palatable food in male or female C57BL/6J mice maintained on ad libitum chow. These findings demonstrate a dissociation between chemotherapy-induced mechanical hypersensitivity and behavioral depression in the assays tested. The transient effects of paclitaxel on operant responding in male C57BL/6J mice may represent a fleeting behavioral correlate of chemotherapy-associated pain-like behaviors in this strain.