Pamplona Fabrício A, Bitencourt Rafael M, Takahashi Reinaldo N
Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário Trindade, 88049-900 Florianópolis, SC, Brazil.
Neurobiol Learn Mem. 2008 Jul;90(1):290-3. doi: 10.1016/j.nlm.2008.04.003. Epub 2008 May 16.
Facilitation of memory extinction by manipulation of the endocannabinoid (eCB) system has been recently studied in several paradigms. Our previous results pointed to facilitation of contextual fear memory extinction by a low dose of a cannabinoid agonist, with a suggestion of short-term effects. The aim of the present study was to further investigate the effects of cannabinoid drugs in the short- and long-term extinction of conditioned fear using an extended extinction protocol. Male Wistar rats were placed in a conditioning chamber and after 3min received a footshock (1.5mA, 1s). On the next day, they received i.p. drug treatment (WIN55212-2 0.25mg/kg, AM404 10mg/kg, SR141716A 1mg/kg) and were re-exposed to the conditioning chamber for 30min (extinction training). No-Extinction groups received the same drug treatment, but were exposed for 3min to the conditioning chamber. A drug-free test of contextual memory (3min) was performed 7 days later. The cannabinoid agonist WI55212-2 and the inhibitor of eCB metabolism/uptake AM404 facilitated short-term extinction. In addition, long-term effects induced by treatments with WIN55212 and AM404 were completely divergent to those of SR141716A treatment. The present results confirm and extend previous findings showing that the eCB system modulates short-term fear memory extinction with long-lasting consequences.
最近在几种实验范式中研究了通过操纵内源性大麻素（eCB）系统来促进记忆消退。我们之前的结果表明，低剂量的大麻素激动剂可促进情境恐惧记忆的消退，并提示有短期效应。本研究的目的是使用延长的消退方案进一步研究大麻素药物在条件性恐惧的短期和长期消退中的作用。将雄性Wistar大鼠置于条件化箱中，3分钟后给予足部电击（1.5mA，1秒）。第二天，它们接受腹腔注射药物治疗（WIN55212-2 0.25mg/kg、AM404 10mg/kg、SR141716A 1mg/kg），并再次暴露于条件化箱中30分钟（消退训练）。非消退组接受相同的药物治疗，但在条件化箱中暴露3分钟。7天后进行无药物的情境记忆测试（3分钟）。大麻素激动剂WI55212-2和eCB代谢/摄取抑制剂AM404促进了短期消退。此外，WIN55212和AM404治疗诱导的长期效应与SR141716A治疗的效应完全不同。目前的结果证实并扩展了先前的发现，即eCB系统调节短期恐惧记忆的消退并产生持久的后果。
