The present study aimed to investigate the possible role of the ventral hippocampal (VH) cannabinoid CB1 receptors in the improving effect of morphine on stress-induced memory formation impairment and anxiety. A step-through type passive avoidance task and a hole-board test were used to measure memory formation and anxiety-like exploratory behavior, respectively. The results showed that the exposure to 10-min stress immediately after the successful training phase impaired memory formation and also produced anxiogenic-like exploratory behaviour in adult male Wistar rats. Moreover, morphine administration before stress exposure improved the adverse effects of stress on memory formation and exploratory behaviour. After training, intra-VH microinjection of cannabinoid CB1/CB2 receptor agonist, WIN 55,212-2 (0.01-0.05 μg/rat) enhanced the response of an ineffective dose of morphine (0.5 mg/kg for memory; 5 mg/kg for anxiety, i.p.) on memory impairment and anxiogenic-like exploratory behaviour induced by acute stress. Intra-VH microinjection of the higher dose of WIN 55,212-2 alone impaired memory formation. Post-training microinjection of a cannabinoid CB1 receptor antagonist/inverse agonist, AM-251 (100-150 ng/rat) into the VH attenuated the response of an effective dose of morphine (5 mg/kg for memory; 6 mg/kg for anxiety, i.p.) in stress-exposed rats. Taken together, the present results showed that morphine administration could improve stress-induced memory impairment and anxiety in the rats exposed to the inescapable acute stress. Interestingly, the improving effect of morphine on the adverse effect of stress on memory formation and anxiety-like exploratory behaviour may be mediated through the VH endocannabinoid CB1/CB2 receptors mechanism.

本研究旨在探讨腹侧海马 (VH) 大麻素 CB1 受体在吗啡改善应激性记忆形成障碍和焦虑的作用中的可能作用。逐步型被动回避任务和洞板测试分别用于测量记忆形成和焦虑样探索行为。结果表明，在成功训练阶段后立即暴露于 10 分钟的压力会损害记忆形成，并且还会在成年雄性 Wistar 大鼠中产生类似焦虑的探索行为。此外，在压力暴露前服用吗啡可改善压力对记忆形成和探索行为的不利影响。训练后，VH 内显微注射大麻素 CB1/CB2 受体激动剂，WIN 55,212-2 (0.01-0. 05 μg/大鼠）增强了无效剂量的吗啡（0.5 mg/kg 用于记忆；5 mg/kg 用于焦虑，腹腔注射）对急性压力引起的记忆障碍和焦虑样探索行为的反应。单独对较高剂量的 WIN 55,212-2 进行 VH 内显微注射会损害记忆形成。训练后将大麻素 CB1 受体拮抗剂/反向激动剂 AM-251（100-150 ng/大鼠）微注射到 VH 中减弱了有效剂​​量的吗啡（5 mg/kg 用于记忆；6 mg/kg 用于记忆）的反应焦虑，ip）在暴露于压力的大鼠中。总之，目前的结果表明，吗啡给药可以改善暴露于不可避免的急性应激的大鼠的应激性记忆障碍和焦虑。有趣的是，