Effects of morphine on spatial learning and memory in Healthy Rats and Streptozotocin Rat Model of Alzheimer's disease

The deposition of β-amyloid in the brain is a pathologicfeature of Alzheimer’s disease (AD).Low doses of morphine, can enhance memory. Theaim of present study,was to investigate the therapeutic efficacy of morphine on memory in Healthy and Streptozotocin (STZ) Rat Model of AD.

In first experiment animals were divided to: Control and Morphine group which were injected with saline and Morphine (5mg/kg, ip) for 10 days. In the second experiment animals were divided to: control, sham operated and groups treated with STZ and STZ plus saline or morphine (2 mg/kg.). For induction of AD, STZ (3 mg/kg, 10 μl/injection site) were administered intolateral ventricles. Morphine or saline, were injected for 10days. All rates were trained in the Morris water maze.

Our results show that chronic injection of Morphine (5mg/kg) impaired spatial learning but improves spatial memory in Healthy rats. our results also show that i.c.v. injection of STZ significantly increased escape latency and Swimming distance to find the hidden platform in comparison with the control group (P<0.05). The amnesic effect of STZ was prevented in rats treated with Low doses of Morphine, So The latency time and Swimming distance to find the platform in the STZ+ Morphine (2 mg/kg) group rats were significantly lower than STZ group (P<0.05). conversely, the percentage of time spent and distance swimming in the target quadrant in theprobe test in the STZ+ Morphine group rats were significantly higher than those in the STZ group.

Higher doses of Morphine, impairs, learning in Healthy rats, whereas Low doses of Morphine, improved , learning and memory in the STZ rat model of AD. The results suggest that treatment with Low doses of Morphine is useful for treatment of cognitive impairment in AD.