Nasehi Mohammad, Piri Morteza, Abbolhasani Kobra, Zarrindast Mohammad R
Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Garmsar Branch, Garmsar, Iran.
Behav Pharmacol. 2013 Jun;24(3):180-94. doi: 10.1097/FBP.0b013e3283618aab.
Bile duct ligation (BDL) is an animal model used in cholestatic disease research. Both opioidergic and nitrergic systems are known to be involved in cholestasis. The aim of this study was to investigate the possible interaction between these two systems in BDL-induced memory formation and exploratory behaviors in mice. Male mice weighing 25-30 g were divided into nonoperated controls, sham-operated, and BDL groups. One-trial step-down and hole-board paradigms were used to assess memory acquisition and exploratory behaviors, respectively. Cholestasis did not alter memory acquisition while increasing exploratory behaviors 7 days after BDL. A pretraining intraperitoneal injection of L-arginine (50, 100, and 200 mg/kg), L-NG-nitroarginine methyl ester (L-NAME) (5, 10, 20, and 40 mg/kg), or naloxone (0.125, 0.25, and 0.5 mg/kg) did not alter memory acquisition or exploratory behaviors, whereas morphine (5 and 7.5 mg/kg) decreased memory acquisition in sham-operated animals. Moreover, although injection of L-NAME and naloxone exerted no effect on memory acquisition in the 7 days post-BDL mice, L-arginine (100 and 200 mg/kg) and morphine (2.5, 5, and 7.5 mg/kg) injection reduced it. In contrast, L-NAME and naloxone, but not morphine or L-arginine, reduced the BDL-induced exploratory behaviors. Coadministration of subthreshold doses of morphine (1.25 mg/kg) and L-arginine (50 mg/kg) caused a memory deficit in 7 days post-BDL mice. However, the memory deficit induced by the effective doses of morphine (2.5 mg/kg) or L-arginine (200 mg/kg) in these mice was restored by the administration of either naloxone (0.5 mg/kg) or L-NAME (40 mg/kg). In addition, naloxone and L-NAME reduced the exploratory behaviors in L-arginine-pretreated mice but not in morphine-pretreated mice. We conclude that there appears to be a synergistic effect between opioidergic and nitrergic systems on memory acquisition and exploratory behaviors in cholestatic mice.
胆管结扎（BDL）是一种用于胆汁淤积性疾病研究的动物模型。已知阿片能系统和一氧化氮能系统均参与胆汁淤积。本研究的目的是探讨这两个系统在BDL诱导的小鼠记忆形成和探索行为中可能存在的相互作用。将体重25 - 30 g的雄性小鼠分为未手术对照组、假手术组和BDL组。分别采用一次性降阶实验和旷场实验范式来评估记忆获得和探索行为。胆汁淤积在BDL后7天增加探索行为的同时，并未改变记忆获得。预训练腹腔注射L - 精氨酸（50、100和200 mg/kg）、L - NG - 硝基精氨酸甲酯（L - NAME）（5、10、20和40 mg/kg）或纳洛酮（0.125、0.25和0.5 mg/kg）均未改变记忆获得或探索行为，而吗啡（5和7.5 mg/kg）使假手术动物的记忆获得减少。此外，虽然注射L - NAME和纳洛酮对BDL后7天小鼠的记忆获得无影响，但注射L - 精氨酸（100和200 mg/kg）和吗啡（2.5、5和7.5 mg/kg）会使其减少。相反，L - NAME和纳洛酮而非吗啡或L - 精氨酸可减少BDL诱导的探索行为。亚阈值剂量的吗啡（1.25 mg/kg）和L - 精氨酸（50 mg/kg）联合给药使BDL后7天的小鼠出现记忆缺陷。然而，这些小鼠中由有效剂量的吗啡（2.5 mg/kg）或L - 精氨酸（200 mg/kg）诱导的记忆缺陷可通过给予纳洛酮（0.5 mg/kg）或L - NAME（40 mg/kg）得以恢复。此外，纳洛酮和L - NAME可减少L - 精氨酸预处理小鼠的探索行为，但对吗啡预处理小鼠无效。我们得出结论，在胆汁淤积小鼠中，阿片能系统和一氧化氮能系统在记忆获得和探索行为上似乎存在协同作用。
