Farahmandfar Maryam, Kadivar Mehdi, Naghdi Nasser, Choopani Samira, Zarrindast Mohammad-Reza
Department of Neuroscience, School of Advanced Medical Technologies, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Behav Brain Res. 2013 Nov 1;256:157-64. doi: 10.1016/j.bbr.2013.07.054. Epub 2013 Aug 1.
In the present study, we investigated the effects of repeated morphine pre-treatment on impairment of spatial memory acquisition induced by intra dorsal hippocampus (intra-CA1) administration of the non-selective cannabinoid CB1/CB2 receptor agonist, WIN55,212-2 in adult male rats. 2-day version of Morris water maze task has been used for the assessment of spatial memory. On the training day, rats were trained by a single training session of eight trials and 24 h later a probe trial test consist of 60s free swim period without a platform and the visible test was administered. Animals received pre-treatment subcutaneous (s.c.) injections of morphine, once daily for three days followed by five days drug-free treatment before training trials. The results indicated that bilateral pre-training intra-CA1 infusions of WIN55,212-2 (0.25 and 0.5 μg/rat) impaired acquisition of spatial memory on the training and test day. The amnesic effect of WIN55, 212-2 (0.5 μg/rat) was prevented in rats previously injected with morphine (20 mg/kg/day × 3 days, s.c.). Improvement in spatial memory acquisition in morphine-pretreated rats was inhibited by once daily administration of naloxone (1 and 2 mg/kg, s.c.) 15 min prior to injection of morphine for three days. The results suggest that sub-chronic morphine treatment may produced sensitization to cannabinoids, which in turn reversed the impairment of spatial memory acquisition induced by WIN55,212-2 and mu- opioid receptors may play an important role in this effect.
在本研究中，我们调查了反复给予吗啡预处理对成年雄性大鼠背侧海马体（CA1区）注射非选择性大麻素CB1/CB2受体激动剂WIN55,212-2所致空间记忆获取障碍的影响。采用2天版的莫里斯水迷宫任务评估空间记忆。在训练日，大鼠接受单次训练，共8次试验，24小时后进行一次探索性试验，该试验包括60秒无平台自由游泳期，并进行可视性测试。动物在训练试验前接受皮下注射吗啡预处理，每天一次，共三天，随后进行五天的无药治疗。结果表明，双侧训练前在CA1区注射WIN55,212-2（0.25和0.5μg/只大鼠）会损害训练日和测试日的空间记忆获取。预先注射吗啡（20mg/kg/天×3天，皮下注射）的大鼠中，WIN55,212-2（0.5μg/只大鼠）的失忆作用得到预防。在注射吗啡前三天，每天一次皮下注射纳洛酮（1和2mg/kg），15分钟前给药，可抑制吗啡预处理大鼠空间记忆获取的改善。结果表明，亚慢性吗啡治疗可能会使机体对大麻素产生敏化作用，进而逆转WIN55,212-2所致的空间记忆获取障碍，且μ-阿片受体可能在这一作用中发挥重要作用。
