Niyuhire Floride, Varvel Stephen A, Thorpe Andrew J, Stokes Rene J, Wiley Jenny L, Lichtman Aron H
Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
Psychopharmacology (Berl). 2007 Apr;191(2):223-31. doi: 10.1007/s00213-006-0650-6. Epub 2007 Jan 9.
Disruption of CB(1) receptor signaling through the use of CB(1) (-/-) mice or the CB(1) receptor antagonist rimonabant (SR141716) has been demonstrated to impair extinction of learned responses in conditioned fear and Morris water maze tasks. In contrast, CB(1) (-/-) mice exhibited normal extinction rates in an appetitively motivated operant conditioning task.
The purpose of this study was to test whether rimonabant would differentially disrupt extinction learning between fear-motivated and food-motivated tasks.
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.
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.
These results support the hypothesis that the CB(1) receptor plays a vital role in the extinction of aversive memories but is not essential for extinction of learned responses in appetitively motivated tasks.
通过使用CB(1)基因敲除小鼠或CB(1)受体拮抗剂利莫那班（SR141716）破坏CB(1)受体信号传导，已被证明会损害条件性恐惧和莫里斯水迷宫任务中习得反应的消退。相比之下，CB(1)基因敲除小鼠在以食欲为动机的操作性条件反射任务中表现出正常的消退率。
本研究的目的是测试利莫那班是否会在恐惧动机任务和食物动机任务之间差异性地破坏消退学习。
将C57BL/6J小鼠分成不同组，分别在两个以厌恶为动机的任务（条件性僵住和被动回避）以及一个以食欲为动机的操作性条件反射任务（固定比率为5的食物强化时间表）中进行训练。习得后，停止每个任务中的相应强化物，并在每次消退训练前30分钟腹腔注射溶剂或利莫那班。
利莫那班（3毫克/千克）处理显著破坏了条件性僵住和被动回避任务中的消退，但无论是使用每日还是每周的消退训练，均未影响操作性条件反射任务中的消退率。有趣的是，利莫那班（3毫克/千克）阻止了操作性条件反射任务首次消退训练期间出现的杠杆按压显著增加（即消退爆发）。
这些结果支持以下假设，即CB(1)受体在厌恶记忆的消退中起重要作用，但对于以食欲为动机的任务中习得反应的消退并非必不可少。
