Pamplona Fabrício Alano, Takahashi Reinaldo Naoto
Departamento de Farmacologia CCB-UFSC, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário Trindade, 88049-900 Florianópolis, SC, Brazil.
Neurosci Lett. 2006;397(1-2):88-92. doi: 10.1016/j.neulet.2005.12.026. Epub 2006 Jan 6.
The memory deficits induced by cannabinoid agonists have been found in several behavioral paradigms. Nevertheless, there is evidence that not all types of memory are impaired after cannabinoid administration. The aim of this study was to investigate whether the cannabinoid agonist WIN 55212-2 (WIN) is able to influence the acquisition of fear conditioning using tone and contextual versions. For tone-fear conditioning, male Wistar rats were placed in the conditioning chamber and after 3 min, a sound (CS) was presented for 10s that terminated with a 1-s electric footshock (1.5 mA). For contextual-fear conditioning, a similar procedure was used but no sound was presented. Twenty-four hours after, the animals were re-exposed to the respective CS (tone or conditioning chamber) and the freezing behavior was registered. A subsequent experiment investigated a possible state-dependent effect of WIN by administering WIN or control solution 30 min before conditioning and before testing. WIN (2.5 and 5.0 mg/kg) administered i.p. 30 min before impaired contextual fear conditioning but did not modify the freezing behavior elicited by tone presentation. These animals did not show any state-dependent effects of WIN. Further, the impaired contextual conditioning was prevented by preadministration of SR141716A (1.0 mg/kg, i.p.) or SR147778 (1.0 mg/kg, i.p.), selective cannabinoid CB1 receptor antagonists. The present findings highlight that cannabinoid agonists effects are selective for the hippocampus-dependent aversive memories in rats. This effect appears to be related to the activation of CB1 cannabinoid receptors and confirms that cannabinoids might provide a novel approach for the treatment of unpleasant memories.
大麻素激动剂诱导的记忆缺陷已在多种行为范式中被发现。然而，有证据表明，给予大麻素后并非所有类型的记忆都会受损。本研究的目的是调查大麻素激动剂WIN 55212-2（WIN）是否能够影响使用音调及情境版本的恐惧条件反射的形成。对于音调恐惧条件反射，将雄性Wistar大鼠置于条件反射箱中，3分钟后，呈现一个持续10秒的声音（条件刺激），随后施加1秒的足部电击（1.5毫安）。对于情境恐惧条件反射，采用类似的程序，但不呈现声音。24小时后，将动物再次暴露于相应的条件刺激（音调或条件反射箱），并记录僵住行为。随后的一项实验通过在条件反射前和测试前30分钟给予WIN或对照溶液，研究了WIN可能的状态依赖性效应。在条件反射前30分钟腹腔注射WIN（2.5和5.0毫克/千克）会损害情境恐惧条件反射，但不会改变音调呈现所引发的僵住行为。这些动物未表现出WIN的任何状态依赖性效应。此外，预先给予选择性大麻素CB1受体拮抗剂SR141716A（1.0毫克/千克，腹腔注射）或SR147778（1.0毫克/千克，腹腔注射）可预防受损的情境条件反射。目前的研究结果表明，大麻素激动剂对大鼠海马体依赖性厌恶记忆具有选择性作用。这种作用似乎与CB1大麻素受体的激活有关，并证实大麻素可能为治疗不愉快记忆提供一种新方法。
