فهرست:
خلاصه فارسی....................................................................................................................................1
فصل اول : کلیات
1-1.ضرورت و اهمیت موضوع............................................................................................................................................3
1-2-بیان مسئله....................................................................................................................................................................3
1-3- اهداف مطالعه............................................................................................................................................................. 4
1-3-1-هدف اصلی.............................................................................................................................................................. 4
1-3-2-اهداف فرعی.............................................................................................................................................................4
فصل دوم : بررسی متون و مطالعات دیگران در این زمینه
2-1-1-یادگیری و حافظه....................................................................................................................................................6
2-1-2 انواع حافظه از نقطه نظر فیزیولوژیک............................................................................................................... 7
2-1-2-1 حافظه آشکار یا صریح.................................................................................................................................. 7
2-1-2-2 حافظه غیرآشکار یا مفهومی......................................................................................................................... 8
2-1-2-3 مراحل شکل گیری حافظه آشکار............................................................................................................... 8
2-1-3- تقسیم بندی حافظه بر اساس زمان................................................................................................9
2-1-4- نواحی مختلف مغزی درگیر در انواع حافظه............................................................................................... 11
2-1-5- تشکیلات هیپوکامپ....................................................................................................................................... 12
2-1-6- تقویت طولانی مدت (LTP).......................................................................................................................... 13
2-1-6-1- مکانسیم های مولکولی شکل پذیری سیناپسی......................................................................................14
2-1-7- یادگیری وابسته به وضعیت..............................................................................................................................17
2-1-8- مطالعات روش های رفتاری حافظه در حیوانات:........................................................................................ 17
2-1-9-1- یادگیری احترازی غیرفعال........................................................................................................................ 18
2-1-9-2- استفاده از تزریق در یادگیری احترازی غیرفعال................................................................................... 19
2-2- سیستم کانابینوئیدی............................................................................................................................................. 19
2-2-1- کانابینوئید ها و اهمیت آنها............................................................................................................................ 19
2-2-2- گیرنده های کانابینوئیدی.................................................................................................................................20
2-2-2-1- جایگاه گیرنده CB1 در CNS.................................................................................................................. 20
2-2-2-3- محل قرارگیری گیرنده CB2................................................................................................................... 21
2-2-2-4 محل قرارگیری CB2 در CNS................................................................................................................ 21
2-2-2-5- پیک های ثانویه گیرنده های کانابینوئیدی................................................................................21
2-2-2-6-آگونیست های گیرنده کانابینوئید................................................................................................. 22
2-2-2-7-انواع اندو کانابینوئید ها................................................................................................................... 23
1-2-2-8- لیگاندهای آندوژن گیرنده های کانابینوئیدی............................................................................ 23
2-2-3- عملکرد اندوکانابینوئید ها به صورت برگشتی................................................................................. 24
2-3- سیستم گلوتاماترژیک و اهمیت ویژه رسپتورهای NMDA....................................................................... 25
2-3-1- L- گلوتامات...................................................................................................................................................... 25
2-3-2- نقش های فیزیولوژیک...................................................................................................................................... 25
2-3-3- ذخایر CNS..................................................................................................................................................... 26
2-3-4- نحوه آزادسازی متابولیسم و ترانسپورتر اختصاصی.................................................................................... 27
2-3-5- انواع گیرنده ها................................................................................................................................................... 28
.2-3-6- سایت ها و عوامل تنظیم کننده.................................................................................................................... 31
2-3-7- آگونیست و آنتاگونیست های اختصاصی..................................................................................................... 33
فصل سوم : مواد و روش ها
3-1-نوع مطالعه و جمعیت مورد مطالعه...................................................................................................................... 36
3-2- مکان انجام آزمایش............................................................................................................................................... 36
3-2-1-حیوان خانه (animal house)........................................................................................................................ 36
3-2-2-اتاق جراحی(Surgery room)....................................................................................................................... 36
3-2-3- اتاق تست رفتاری.............................................................................................................................................. 37
3-3- زمان انجام آزمایشات............................................................................................................................................ 37
3-4-محدودیت ها............................................................................................................................................................. 37
3-4- ملاحظات اخلاقی................................................................................................................................................... 37
3-6-مواد و روش ها........................................................................................................................................................ 37
3-6-1-وسایل و دستگاه های مورد نیاز...................................................................................................................... 37
3-6-2-مواد و داروهای مورد استفاده........................................................................................................................... 38
3-8- دستگاه بررسی حافظه( Step-Through)........................................................................................................ 39
3-9- حیوانها....................................................................................................................................................................... 40
3-10- مراحل جراحی...................................................................................................................................................... 40
3-11- تزریق درون مغزی دارو...................................................................................................................................... 45
3-12- تستهای رفتاری................................................................................................................................................... 46
3-12-1 مرحله آموزش................................................................................................................................................... 46
3-12-2- مرحله آزمون یا بررسی حافظه.................................................................................................................... 47
3-13- تیمار های دارویی و آزمایشهای انجام شده........................................................................................... 48
3-13-1- آزمایش شماره 2: بررسی تاثیر تزریق پس از آموزش AM630 بر روی حافظه ی اجتنابی مهاری (نمودار Dose response)............................................................................................................................................... 48
3-13-2- آزمایش شماره 3: بررسی تاثیر تزریق پس از آموزش GP1a بر روی حافظه ی اجتنابی مهاری (نمودار Dose response)............................................................................................................................................... 49
3-13-3- آزمایش شماره 1: بررسی تاثیر تزریق پس از آموزش D-AP5 بر روی حافظه ی اجتنابی مهاری (نمودار Dose response)................................................................................................................................................ 49
3-13-4- آزمایش شماره 4: بررسی تاثیر تزریق دوز غیر موثرAM630 بر حافظه موشهای تیمار شده با D-AP5................................................................................................................................................................................. 50
3-13-5- آزمایش شماره 5: بررسی تاثیر تزریق دوز غیر موثرGP1a بر حافظه موش های تیمار شده با D-AP5............................................................................................................................................................................... 50
فصل چهارم : نتایج
4-1- بررسی تاثیر تزریق پس از آموزشD-AP5 بر روی حافظه اجتنابی مهاری............................................ 54
4-2- بررسی تاثیر تزریق پس از آموزشAM630 بر روی حافظه اجتنابی مهاری........................................... 56
4-3- بررسی تاثیر تزریق پس از آموزشGP1a بر روی حافظه اجتنابی مهاری...................................................58
4-4- بررسی تاثیر تزریق پس از آموزشAM630 برحافظه موش های تیمار شده با D-AP5...........................60
4-5- بررسی تاثیر تزریق پس از آموزشGP1a بر روی حافظه موشهای تیمار شده با D-AP5.....................61
فصل پنجم : بحث و نتیجه گیری
5-1- سیستم گلوتاماتارژیک در هیپوکامپ و اهمیت آن درتثیبت حافظه............................................................65
5-2-سیستم کانابینوئیدی و اهمیت آن درتثبیت حافظه.......................................................................................... 67
5-3-بررسی تداخل سیستم کانابینوئیدی و سیستم گلوتاماتی در تثبیت حافظه............................................... 68
نتیجه گیری........................................................................................................................................................................ 70
پیشنهادات................................................................................................................................................... 72
خلاصه انگلیسی.........................................................................................................................................73
منابع...................................................................................................................................................74
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