The disruptive effects of the CB1 receptor antagonist rimonabant on extinction learning in mice are task-specific
The disruptive effects of the CB1 receptor antagonist rimonabant on extinction learning in mice are task-specific
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DOI：
10.1007/s00213-006-0650-6
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发表时间：
2007-04-01
影响因子：
3.4
通讯作者：
Lichtman, Aron H.
中科院分区：
文献类型：
--
作者：
Niyuhire, Floride;Varvel, Stephen A.;Lichtman, Aron H.
原理已证明，通过使用CB 1（-/-）小鼠或CB 1受体拮抗剂利莫那班（SR 141716）破坏CB 1受体信号传导可损害条件性恐惧和Morris水迷宫任务中学习反应的消退。相反，CB 1（-/-）小鼠在食欲动机的操作性条件反射任务中表现出正常的消退率。目的本研究的目的是测试利莫那班是否会在恐惧动机和食物动机的任务中不同地破坏消退学习。材料和方法将不同组的C57 BL/6 J小鼠训练在两个厌恶动机的任务中，条件冻结和被动回避，和一个食欲动机的操作性条件反射任务在一个固定的比例（FR-5）的时间表的食物强化。收购后，在每个任务中的各自的precurcers被扣留，和腹膜内注射的车辆或利莫那班给予30分钟前，每个extinction semination.Results利莫那班（3 mg/kg）治疗显着中断灭绝的条件冻结和被动回避任务，但未能影响灭绝率的操作性条件反射任务，无论是使用每天或每周的灭绝会议。有趣的是，利莫那班（3 mg/kg）防止了杠杆按压的显著增加（即，结论这些结果支持了CB 1受体在厌恶性记忆消退中起重要作用的假设，但在食欲动机任务中对学习反应的消退不是必需的。
Rationale Disruption of CB1 receptor signaling through the use of CB1 (-/-) mice or the CB1 receptor antagonist rimonabant (SR141716) has been demonstrated to impair extinction of learned responses in conditioned fear and Morris water maze tasks. In contrast, CB1 (-/-) mice exhibited normal extinction rates in an appetitively motivated operant conditioning task.Objectives The purpose of this study was to test whether rimonabant would differentially disrupt extinction learning between fear-motivated and food-motivated tasks.Materials and methods Separate groups of C57BL/6J mice were trained in two aversively motivated tasks, conditioned freezing and passive avoidance, and an appetitively motivated operant conditioning task at a fixed ratio (FR-5) schedule of food reinforcement. After acquisition, the respective reinforcers in each task were withheld, and an intraperitoneal injection of vehicle or rimonabant was given 30 min before each extinction session.Results Rimonabant (3 mg/kg) treatment significantly disrupted extinction in both the conditioned freezing and passive avoidance tasks but failed to affect extinction rates in the operant conditioning task, whether using daily or weekly extinction sessions. Interestingly, rimonabant (3 mg/kg) prevented the significant increases in lever pressing (i.e., extinction burst) that occurred during the first extinction session of the operant conditioning task.Conclusions These results support the hypothesis that the CB1 receptor plays a vital role in the extinction of aversive memories but is not essential for extinction of learned responses in appetitively motivated tasks.