BACKGROUND & AIMS:
: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.
背景与目标:
: 在本研究中,我们研究了重复吗啡预处理对非选择性大麻素CB1/CB2受体激动剂WIN55、212-2在成年雄性大鼠中给予背海马 (intra-CA1) 引起的空间记忆获取障碍的影响。莫里斯水迷宫任务的2天版本已用于评估空间记忆。在训练当天,对大鼠进行了八次试验的单次训练,24小时后进行了一次探针试验测试,该试验包括60s的自由游泳期,没有平台,并进行了可见测试。动物接受治疗前皮下注射吗啡,每天一次,持续三天,然后在训练试验前进行五天的无药治疗。结果表明,在训练和测试当天,双侧训练前intra-CA1输注WIN55,212-2 (0.25和0.5 μ g/大鼠) 会损害空间记忆的获取。在先前注射吗啡 (20 mg/kg/天 × 3天,s.C.) 的大鼠中预防WIN55,212-2 (0.5 μ g/大鼠) 的遗忘作用。每天服用一次纳洛酮 (1和2 mg/kg,s.C.) 可抑制吗啡预处理大鼠空间记忆的获取。注射吗啡前15分钟,持续三天。结果表明,亚慢性吗啡治疗可能会产生对大麻素的敏感性,从而逆转由WIN55,212-2和mu-阿片受体引起的空间记忆获取障碍可能在这种作用中起重要作用。