Facilitation of contextual fear memory extinction and anti-anxiogenic effects of AM404 and cannabidiol in conditioned rats
Facilitation of contextual fear memory extinction and anti-anxiogenic effects of AM404 and cannabidiol in conditioned rats
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DOI：
10.1016/j.euroneuro.2008.07.001
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发表时间：
2008-12-01
影响因子：
5.6
通讯作者：
Takahashi, Reinaldo N.
中科院分区：
文献类型：
--
作者：
Bitencourt, Rafael M.;Pamplona, Fabricio A.;Takahashi, Reinaldo N.
本研究探讨了eCB摄取/代谢抑制剂AM404和植物大麻素大麻二酚（CBD）对大鼠背景恐惧记忆消退的中枢作用。大鼠进行条件化，24小时后进行三个连续的9分钟非强化暴露的条件（灭绝会议，24小时间隔）。AM404或CBD在每次消退前5分钟静脉内注射，并在最后一次消退后24小时进行3分钟无药物背景记忆测试。AM404（1.0 μ g/μ l，i.c.v.）和CBD（2.0 μ g/μ l，i.c.v.）促进背景恐惧记忆的消退，具有持续的影响。这些反应被CB 1选择性拮抗剂SR 141716 A（0.2 mg/kg，i. p.）拮抗，但不被TRPV 1选择性拮抗剂辣椒平（5.0 μ g/μ l，i. c. v.）抗焦虑药物地西泮（DZP）对背景恐惧记忆消退的影响也进行了研究。与CBD和AM404的结果相反，DZP诱导的条件冻结的表达普遍减少。AM404和CBD在恐惧增强的十字迷宫试验中均诱导抗焦虑作用，而DZP在条件和非条件大鼠中具有抗焦虑作用。总之，CBD，一种非精神活性的植物大麻素，可能是一种有趣的药理学方法，可以减少压力的焦虑作用，促进恐惧记忆的消失。(C)2008 Elsevier B.V.和ECNP。All rights reserved.
The present study investigated the central effects of the eCB uptake/metabolism inhibitor AM404 and the phytocannabinoid cannabidiol (CBD) on the extinction of contextual fear memories in rats. Rats were conditioned and 24 h later subjected to three consecutive 9-min non-reinforced exposures to the conditioning context (extinction sessions, 24 h intervals). AM404 or CBD was injected i.c.v. 5 min before each extinction session and a 3-min drug-free test of contextual memory was performed 24 h after the last extinction session. AM404 (1.0 mu g/mu l, i.c.v.) and CBD (2.0 mu g/mu l, i.c.v.) facilitated extinction of contextual fear memory, with persistent effects. These responses were antagonized by the CB1-selective antagonist SR141716A (0.2 mg/kg, i.p.), but not by the TRPV1-selective antagonist capsazepine (5.0 mu g/mu l, i.c.v.). The effect of the anxiolytic drug Diazepam (DZP) on the extinction of contextual fear memory was also investigated. In contrast with the CBD and AM404 results, DZP induced a general reduction in the expression of conditioned freezing. Both AM404 and CBD induced anti-anxiogenic effect in the fear-potentiated plus-maze test, whereas DZP was anxiolytic in conditioned and unconditioned rats. In conclusion, CBD, a non-psychoactive phytocannabinoid could be an interesting pharmacological approach to reduce the anxiogenic effects of stress and promote the extinction of fear memories. (C) 2008 Elsevier B.V. and ECNP. All rights reserved.