A comparison between usual and ultra low doses of morphine combined with forced swim stress, on memory retention in rat

‎ Introduction: Controversial results have been reported about the effect of morphine and stress on learning and spatial memory in rodents. There are very few studies about the effects of ultra low doses of morphine on memory. In this study, effects of acute administration of low and usual doses of morphine on memory formation and retention in the presence and absence of repeated stress were investigated. Methods: adult male Wistar rats (200-250g) were divided into 3 groups A) Rats were trained for 4 constitutive days and then intraperitoneally received different doses of morphine (1μg/kg, 10μg/kg, 100μg/kg, 1mg/kg and 10mg/kg) 30 minutes before retention test on the 5th day. B) Animals experienced forced swimming stress 30 minutes before each training session for 4 constitutive days and memory retention was evaluated on the 5th and 12th days. C) Rats were treated like animals in group B and then like group A. In all groups, retention tests were done without any excessive treatment on the 12th day. Escape latency and mean path length from the starting point to the platform on training days were considered as learning parameters, while time spent in the target quadrant on the 5th and 12th days was regarded as retention parameter. Results: Memory retention was decreased with 1 μg/kg and 10 mg/kg doses of morphine on the 5th day (P<0.001). Repeated stress led to decreased learning (P<0.001) and retention on the 5th and 12th days (P<0.05). In animals treated with both repeated stress and acute morphine (except for the dose of 1 mg/kg) retention decreased on the 5th day (p<0.001), while retention diminished for all groups on the 12th day. Conclusion: Morphine at usual dose of 10 mg/kg may cause memory retention impairment, by its inhibitory action on the opioidergic system. Surprisingly, morphine at ultra low dose (1 μg/kg) has the same effect and the excitatory action of opioidergic system may be responsible for this effect, however it needs further studies. Repeated stress in combination with morphine even at ineffective dosage could cause memory impairment in the Morris water maze, so the presence of both factors, can probably cause additive impairment of memory