Abstract：
Cancer patients often experience anticipatory nausea and vomiting (ANV) due to Pavlovian conditioning. Both N-methyl-D-aspartate and beta-adrenergic receptors are known to mediate memory formation, but their role in the development of ANV remains unclear. This study used a conditioned context aversion (CCA) paradigm, an animal model for ANV, to assess whether administration of the beta-adrenergic receptor antagonist propranolol or the N-methyl-D-aspartate receptor antagonist MK-801 immediately after CCA training has an effect on the later expression of CCA in CD1 male mice. In experiment 1, three groups were injected with lithium chloride (LiCl) to induce aversion in a novel context, resulting in CCA. A control group was injected with sodium chloride (NaCl). Following conditioning, two of the LiCl-treated groups received different doses of MK-801 (0.05 or 0.2 mg/kg), while the remaining LiCl-treated and NaCl-treated groups received a second NaCl injection. In experiment 2, two groups were injected with LiCl, and one group was injected with NaCl. After conditioning, one of the LiCl-treated groups received a propranolol injection (10 mg/kg). The remaining LiCl-treated and NaCl-treated groups received NaCl injections. Water consumption was measured in all groups 72 h later within the conditioning context. Postconditioning administration of propranolol, but not MK-801, attenuated CCA, as revealed by similar levels of water consumption in animals that received LiCl and propranolol relative to NaCl-treated animals. These findings suggest that beta-adrenergic receptor activation is crucial for the development of CCA. Therefore, propranolol may represent a novel therapeutic approach for cancer patients at high risk of ANV.
摘要：
由于巴甫洛夫调节，癌症患者经常会出现预期的恶心和呕吐（ANV）。已知N-甲基-D-天冬氨酸和β-肾上腺素能受体都介导记忆形成，但它们在ANV发展中的作用尚不清楚。这项研究使用了条件语境厌恶(CCA)范式，ANV的动物模型,评估CCA训练后立即给予β-肾上腺素能受体拮抗剂普萘洛尔或N-甲基-D-天冬氨酸受体拮抗剂MK-801是否对CD1雄性小鼠CCA的后期表达有影响。在实验1中，三组注射氯化锂（LiCl）以在新的背景下诱导厌恶，导致CCA。对照组注射氯化钠(NaCl)。调节后,两个LiCl治疗组接受不同剂量的MK-801（0.05或0.2mg/kg），其余LiCl处理组和NaCl处理组接受第二次NaCl注射。在实验2中，两组注射LiCl，一组注射NaCl。调理后,其中一个LiCl治疗组接受了普萘洛尔注射液(10mg/kg).剩余的LiCl处理组和NaCl处理组接受NaCl注射。72小时后在条件条件下测量所有组的水消耗。普萘洛尔的后处理给药，但不是MK-801，衰减的CCA，与接受NaCl处理的动物相比，接受LiCl和普萘洛尔的动物的水消耗水平相似。这些发现表明，β-肾上腺素能受体的激活对于CCA的发展至关重要。因此,对于ANV高危癌症患者,普萘洛尔可能是一种新的治疗方法.
