Differential effect of morphine on spatial learning and memory in rat model of streptozotocin-induced dementia of Alzheimer's type

摘要

Introduction: Alzheimer’s disease (AD) is characterized by the accumulation of intra and extracellular amyloid-β(Aβ) plaques, and hyperphosphorylated Tau protein and synapticeuronal loss. Certain experimental models supportmorphine can play a beneficial role against damage in the neuronal system. It has been shown that morphineapplication immediately after hypoxia decreases infarction volume in the rat brain of hypoxia–ischemia model.Theaim of present study, was to investigate the therapeutic efficacy of morphine on learning and memory instreptozotocin (STZ) Rat Model of AD.Methods: 60 male Wistar rats were divided to: control, vehicle and groups treated with STZ and STZ plus saline ormorphine. For induction of AD, STZ (3 mg/kg, 10 μl/injection site) wereadministered bilaterally into lateralventricles.Morphine (1, 2.5 and 5 mg/kg, i.p.) or saline (0.2ml), were injected daily, one week after operation for10days before training. All rates were trained in the Morris water maze (MWM) 3 weeks after stereotaxic operation.On the training days, rats were given a daily session of 4 trials per day for 6 consecutive days, 24 h after the lastacquisition session, a ‘probe trial’ was used to assess the spatial memory.Results: The results indicated thati.c.v. injection of STZ significantly increased escape latency and Swimmingdistance to find the hidden platform in comparison with the control and saline groups (P<0.05). The amnesic effect ofSTZ was prevented in rats treated with Low doses of Morphine (1 and 2.5 mg/kg/day) whereas treatment with highdoses of Morphine (5 mg/kg) led to further impairment of learning and memory in the STZ rat model of sporadic AD.So The latency time and Swimming distance to find the platform in the Morphine (2.5 mg/kg) group rats weresignificantly lower than those in the other STZ-induced AD groups (P<0.05) conversely, the percentage of time spentand distance swimming in the target quadrant in the STZ+Morphine (2.5 mg/kg) group rats were significantly higherthan those in the other STZ-induced AD groups (P<0.001).Conclusion: Our data show that Low doses of Morphine(1 and 2.5 mg/kg), facilitates, whereas higher doses ofMorphine(5 mg/kg), impairs, learning and memory in STZ-induced rat model of sporadic AD.The results suggest thatchronic treatment with Low doses of Morphine can play a beneficial role against damage in the neuronal system,which in turn reversed the impairment of spatial memory acquisition induced by i.c.v. injection of STZ.