اثرات مرفين بر يادگيري و حافظة فضايي موش هاي سالم و آلزايمري مدل استرپتوزوتوسين

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

زﻣﯿﻨﻪ و ﻫﺪف ر ﺳﻮب آﻣﯿﻠﻮﺋﯿﺪﻫﺎي ﺑﺘﺎ در ﻣﻐﺰ ﯾﮑﯽ از وﯾﮋﮔﯽﻫﺎي ﭘﺎﺗﻮﻟﻮژﯾﮏ ﺑﯿﻤﺎري آﻟﺰاﯾﻤﺮ ا ﺳﺖ. دوزﻫﺎي ﭘﺎﯾﯿﻦ ﻣﺮﻓﯿﻦ ﻣﯽﺗﻮاﻧﺪ ﺣﺎﻓﻈﻪ را اﻓﺰاﯾﺶ دﻫﺪ. ﻫﺪف از ﭘﮋوﻫﺶ ﺣﺎﺿﺮ، ﺑﺮرﺳﯽ اﺛﺮﺑﺨﺸﯽ درﻣﺎن ﻣﺮﻓﯿﻦ ﺑﺮ ﺣﺎﻓﻈﮥ ﻣﻮشﻫﺎي ﺳﺎﻟﻢ و آﻟﺰاﯾﻤﺮي ﻣﺪل اﺳﺘﺮﭘﺘﻮزوﺗﻮﺳﯿﻦ ﺑﻮد. ﻣﻮاد و روشﻫﺎ در آزﻣﺎﯾﺶ اول ﺣﯿﻮاﻧﺎت ﺑﻪ ﮔﺮوه ﺷﺎﻫﺪ و ﻣﺮﻓﯿﻦ ﺗﻘﺴﯿﻢ ﺷﺪﻧﺪ ﮐﻪ ﺳﺎﻟﯿﻦ و ﻣﺮﻓﯿﻦ)5 ﻣﯿﻠﯽﮔﺮم ﺑﺮ ﮐﯿﻠﻮﮔﺮم، داﺧﻞ ﺻﻔﺎﻗﯽ( ﺑﻪﻣﺪت 10 روز ﺑﻪ آنﻫﺎ ﺗﺰرﯾﻖ ﺷﺪ. در آزﻣﺎﯾﺶ دوم ﺣﯿﻮاﻧﺎت ﺑﻪ ﮔﺮوه ﺷﺎﻫﺪ، ﺷﻢ، ﮔﺮوهﻫﺎي ﺗﺤﺖ درﻣﺎن ﺑﺎ اﺳﺘﺮﭘﺘﻮزوﺗﻮﺳﯿﻦ و اﺳﺘﺮﭘﺘﻮزوﺗﻮﺳﯿﻦ ﺑﻪ ﻫﻤﺮاه ﺳﺎﻟﯿﻦ ﯾﺎ ﻣﺮﻓﯿﻦ)2 ﻣﯿﻠﯽﮔﺮم ﺑﺮ ﮐﯿﻠﻮﮔﺮم( ﺗﻘﺴﯿﻢ ﺷﺪﻧﺪ. ﺑﺮاي اﯾﺠﺎد اﻟﺰاﯾﻤﺮ اﺳﺘﺮﭘﺘﻮزوﺗﻮﺳﯿﻦ)3ﻣﯿﻠﯽﮔﺮم ﺑﺮﮐﯿﻠﻮﮔﺮم ، 10ﻣﯿﮑﺮوﻟﯿﺘﺮ در ﻣﺤﻞ ﺗﺰرﯾﻖ( ﺑﻪ داﺧﻞ ﺑﻄﻦﻫﺎي ﻃﺮﻓﯽ ﻣﻐﺰ ﺗﺰرﯾﻖ ﺷﺪ. ﻣﺮﻓﯿﻦ ﯾﺎ ﺳﺎﻟﯿﻦ ﺑﺮاي ﻣﺪت 10 روز ﺗﺰرﯾﻖ ﺷﺪ. ﻫﻤﮥ ﻣﻮشﻫﺎ در ﻣﺎز آﺑﯽ آﻣﻮزش داده ﺷﺪﻧﺪ. ﯾﺎﻓﺘﻪﻫﺎ ﻧﺘﺎﯾﺞ ﭘﮋوﻫﺶ ﺣﺎﺿﺮ ﻧﺸﺎن داد ﮐﻪ ﺗﺰرﯾﻖ ﻣﺰﻣﻦ ﻣﺮﻓﯿﻦ)5 ﻣﯿﻠﯽﮔﺮم ﺑﺮ ﮐﯿﻠﻮﮔﺮم( ﺑﺎﻋﺚ اﺧﺘﻼل در ﯾﺎدﮔﯿﺮي ﻓﻀﺎﯾﯽ ﻣﯽﺷﻮد؛ اﻣﺎ ﺣﺎﻓﻈﮥ ﻓﻀﺎﯾﯽ را در ﻣﻮشﻫﺎي ﻧﺮﻣﺎل ﺑﻬﺒﻮد ﻣﯽﺑﺨﺸﺪ، ﻧﯿﺰ ﺗﺰرﯾﻖ داﺧﻞ ﺑﻄﻨﯽ اﺳﺘﺮﭘﺘﻮزوﺗﻮﺳﯿﻦ ﺑﺎﻋﺚ اﻓﺰاﯾﺶ ﻣﻌﻨﺎدار ﺗﺄﺧﯿﺮ زﻣﺎﻧﯽ و ﻓﺎﺻﻠﮥ ﺷﻨﺎﮐﺮدن ﺑﺮاي ﯾﺎﻓﺘﻦ ﺳﮑﻮ در ﻣﻘﺎﯾﺴﻪ ﺑﺎ ﮔﺮوه ﺷﺎﻫﺪ ﻣﯽﺷﻮد)0/05< P(. از اﺛﺮﻫﺎي ﻓﺮاﻣﻮﺷﯽآور اﺳﺘﺮﭘﺘﻮزوﺗﻮﺳﯿﻦ ﺑﺎ ﺗﺰرﯾﻖ دوز ﮐﻢ ﻣﺮﻓﯿﻦ ﭘﯿﺸﮕﯿﺮي ﺷﺪ؛ ﭼﻨﺎنﮐﻪ ﺗﺄﺧﯿﺮ زﻣﺎﻧﯽ و ﻣﺴﺎﻓﺖ ﻃﯽﺷﺪه ﺑﺮاي ﯾﺎﻓﺘﻦ ﺳﮑﻮ در ﮔﺮوه اﺳﺘﺮﭘﺘﻮزوﺳﯿﻦ + ﻣﺮﻓﯿﻦ )2 ﻣﯿﻠﯽﮔﺮم ﺑﺮ ﮐﯿﻠﻮﮔﺮم( ﺑﻪﻃﺮز ﻣﻌﻨﺎداري ﮐﻤﺘﺮ از ﮔﺮوه اﺳﺘﺮﭘﺘﻮزوﺗﻮﺳﯿﻦ ﺑﻮد)0/05< P(. ﺑﺮﻋﮑﺲ، درﺻﺪ زﻣﺎن ﺳﭙﺮيﺷﺪه و ﻣﺴﺎﻓﺖ ﻃﯽﺷﺪه در رﺑﻊ ﻫﺪف در ﺗﺴﺖ ﭘﺮوب در ﮔﺮوه اﺳﺘﺮﭘﺘﻮزوﺗﻮﺳﯿﻦ + ﻣﺮﻓﯿﻦ ﺑﻪﻃﺮز ﻣﻌﻨﺎداري ﺑﯿﺸﺘﺮ از ﮔﺮوه اﺳﺘﺮﭘﺘﻮزوﺗﻮﺳﯿﻦ ﺑﻮد. ﻧﺘﯿﺠﻪﮔﯿﺮي دوزﻫﺎي ﺑﺎﻻﯾﯽ ﻣﺮﻓﯿﻦ ﯾﺎدﮔﯿﺮي را در ﻣﻮشﻫﺎي ﻧﺮﻣﺎل ﻣﺨﺘﻞ ﻣﯽﮐﻨﺪ؛ درﺣﺎﻟﯽﮐﻪ دوزﻫﺎي ﭘﺎﯾﯿﻦ ﻣﺮﻓﯿﻦ ﯾﺎدﮔﯿﺮي و ﺣﺎﻓﻈﻪ را در ﻣﻮشﻫﺎي آﻟﺰاﯾﻤﺮي ﻣﺪل اﺳﺘﺮﭘﺘﻮزوﺗﻮﺳﯿﻦ ﺑﻬﺒﻮد ﻣﯽﺑﺨﺸﺪ. ﻧﺘﺎﯾﺞ ﻧﺸﺎن ﻣﯽدﻫﺪ ﮐﻪ درﻣﺎن ﺑﺎ دوز ﮐﻢ ﻣﺮﻓﯿﻦ ﺑﺮاي درﻣﺎن اﺧﺘﻼلﻫﺎي ﺷﻨﺎﺧﺘﯽ در ﺑﯿﻤﺎران آﻟﺰاﯾﻤﺮي ﻣﻔﯿﺪ اﺳﺖ.

Introduction: The deposition of β-amyloid in the brain is a pathologic feature of Alzheimer’s disease (AD). Low doses of morphine, can enhance memory. The aim of present study, was to investigate the therapeutic efficacy of morphine on memory in Healthy and Streptozotocin (STZ) Rat Model of AD. Materials and Methods: 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 into lateral ventricles. Morphine or saline, were injected for 10days. All rates were trained in the Morris water maze. Results: 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 the probe test in the STZ+ Morphine group rats were significantly higher than those in the STZ group. Conclusion: 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.