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研究生:廖芷稜
研究生(外文):Chih-leng Liao
論文名稱:連續甲基安非他命注射影響小鼠空間記憶提取及相關MAPK活化之研究
論文名稱(外文):Effect of repeated methamphetamine administration on retrieval of spatial memory and associated activation of MAPK (mitogen-activated protein kinase) in mice
指導教授:劉怡均劉怡均引用關係
指導教授(外文):Ingrid Y.C. Liu
學位類別:碩士
校院名稱:慈濟大學
系所名稱:神經科學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
畢業學年度:96
語文別:英文
論文頁數:52
中文關鍵詞:空間記憶提取甲基安非他命
外文關鍵詞:MAPKspatial memoryretrievalmethamphetamine
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甲基安非它命在台灣是最常見的濫用藥物,它是一種 psychostimulatant, 常被拿來治療兒童 attention deficit hyperactivity disorder (ADHD). 短期使用甲基安非它命有高度提神效果,使疲勞感消失、活動力增加;長期使用安非他命則造成依賴性及成癮性。過去有許多的研究指出甲基安非它命會影響長期空間記憶,究竟是促進記憶還是損害記憶目前仍無定論 。因此本論文旨在探討長期投予甲基安非它命對空間記憶的影響,以及其分子機制。我利用依賴海馬回的莫氏水迷宮作為動物行為測定之模型,長期投予連續7天甲基安非它命,比較老鼠在注射甲基安非它命之前及之後在莫氏水迷宮的表現情形,發現投予甲基安非它命的組別不管在hidden platform test 或 probe trial test的表現都較好。接著我再利用西方點墨法和免疫組織化學法證明在海馬迴和小腦中磷酸化 MAPK 中的 Erk 1/2 路徑與增強空間記憶的提取相關,但p38 路徑則較無關係。最後從免疫螢光染色中看到 p-Erk 和 tyrosine hydroxylase 在海馬迴有共同表現在相同細胞的現象,這證明了連續投予甲基安非他命而增進空間記憶的提取是經由 Erk 在海馬迴中 dopaminergic neurons的活化。至於,小腦中 Erk活化程度的增加是在何種神經元,則必須更進一步實驗確認。
Methamphetamine (METH) is a popular abused drug in Taiwan. It is also a psychositmulant and often used to treat childhood attention deficit hyperactivity disorder (ADHD). Short-term abuse of methamphetamine can cause high wake up, lower fatigue and increase locomotor activity. Long-term abuse of methamphetamine, on the other hand, results in dependence and addiction. Many studies indicated that METH could influence long-term spatial memory, however, results were controversial. It is not clear yet whether METH would enhance or impair spatial memory. In the present study, I investigated the effect of repeated METH administration on performance of long-term spatial memory and its underlying signaling pathway. I used hippocampal-dependent Morris water maze paradigm to study the effect of METH on performance of spatial memory. The mice were administered with METH for 7 consecutive days. Compared with statuses before and after METH injection, my data showed that METH treated groups performed better than saline groups in both hidden platform and probe trial tests. Further, I used Western blotting and immunohistochemistry to demonstrate that enhanced retrieval of spatial memory by repeated METH treatment was through increased phospho-Erk pathway in the hippocampus and cerebellum but independent on p38 pathway. Finally, I used immunofluorescent staining to prove that p-Erk and tyrosine hydroxylase were colocalized in the hippocampus but in not the cerebellum. That is, Erk signaling was activated in dopaminergic neurons of the hippocampus but in other types of cells in the cerebellum.
Introduction………………………………………………1

Materials and Methods…………………………………10

Results…………………………………………………...16

Discussion………………………………………………..21

Figures…………………………………………………...24

References……………………………………………….51
Abel T, Lattal KM (2001) Molecular mechanisms of memory acquisition, consolidation and retrieval. Curr Opin Neurobiol 11:180-187.
Anglin MD, Burke C, Perrochet B, Stamper E, Dawud-Noursi S (2000) History of the methamphetamine problem. J Psychoactive Drugs 32:137-141.
Arbabi S, Maier RV (2002) Mitogen-activated protein kinases. Crit Care Med 30:S74-S79.
Blum S, Moore AN, Adams F, Dash PK (1999) A mitogen-activated protein kinase cascade in the CA1/CA2 subfield of the dorsal hippocampus is essential for long-term spatial memory. J Neurosci 19:3535-3544.
Bogoyevitch MA, Court NW (2004) Counting on mitogen-activated protein kinases--ERKs 3, 4, 5, 6, 7 and 8. Cell Signal 16:1345-1354.
Bolshakov VY, Carboni L, Cobb MH, Siegelbaum SA, Belardetti F (2000) Dual MAP kinase pathways mediate opposing forms of long-term plasticity at CA3-CA1 synapses. Nat Neurosci 3:1107-1112.
D'Hooge R, De Deyn PP (2001) Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev 36:60-90.
Elliott JM, Beveridge TJ (2005) Psychostimulants and monoamine transporters: upsetting the balance. Curr Opin Pharmacol 5:94-100.
Feldman RS, Meyer JS, Quenzer LF (1997) Principles of neuropsychopharmacology. pp.549-568.
Freese TE, Miotto K, Reback CJ (2002) The effects and consequences of selected club drugs. J Subst Abuse Treat 23:151-156.
Glickstein SB, Hof PR, Schmauss C (2002) Mice lacking dopamine D2 and D3 receptors have spatial working memory deficits. J Neurosci 22:5619-5629.
Kales A, Cadieux R, Soldatos CR, Tan TL (1979) Successful treatment of narcolepsy with propranolol: a case report. Arch Neurol 36:650-651.
Maekawa M, Watanabe M, Yamaguchi S, Konno R, Hori Y (2005) Spatial learning and long-term potentiation of mutant mice lacking D-amino-acid oxidase. Neurosci Res 53:34-38.
Matsumoto T, Kamijo A, Yamaguchi A, Iseki E, Hirayasu Y (2005) Childhood histories of attention-deficit hyperactivity disorders in Japanese methamphetamine and inhalant abusers: preliminary report. Psychiatry Clin Neurosci 59:102-105.
McDonald RJ, Hong NS, Devan BD (2004) The challenges of understanding mammalian cognition and memory-based behaviours: an interactive learning and memory systems approach. Neurosci Biobehav Rev 28:719-745.
Miyamoto Y, Chen L, Sato M, Sokabe M, Nabeshima T, Pawson T, Sakai R, Mori N (2005) Hippocampal synaptic modulation by the phosphotyrosine adapter protein ShcC/N-Shc via interaction with the NMDA receptor. J Neurosci 25:1826-1835.
Pereira FC, Imam SZ, Gough B, Newport GD, Ribeiro CF, Slikker W, Jr., Macedo TR, Ali SF (2002) Acute changes in dopamine release and turnover in rat caudate nucleus following a single dose of methamphetamine. J Neural Transm 109:1151-1158.
Rawson RA, Gonzales R, Brethen P (2002) Treatment of methamphetamine use disorders: an update. J Subst Abuse Treat 23:145-150.
Schimanski LA, Nguyen PV (2004) Multidisciplinary approaches for investigating the mechanisms of hippocampus-dependent memory: a focus on inbred mouse strains. Neurosci Biobehav Rev 28:463-483.
Sulzer D, Sonders MS, Poulsen NW, Galli A (2005) Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol 75:406-433.
Thomas GM, Huganir RL (2004) MAPK cascade signalling and synaptic plasticity. Nat Rev Neurosci 5:173-183.
Viggiano D, Ruocco LA, Sadile AG (2003) Dopamine phenotype and behaviour in animal models: in relation to attention deficit hyperactivity disorder. Neurosci Biobehav Rev 27:623-637.
Volkow ND, Chang L, Wang GJ, Fowler JS, Leonido-Yee M, Franceschi D, Sedler MJ, Gatley SJ, Hitzemann R, Ding YS, Logan J, Wong C, Miller EN (2001) Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. Am J Psychiatry 158:377-382.
White NM, Salinas JA (2003) Mnemonic functions of dorsal striatum and hippocampus in aversive conditioning. Behav Brain Res 142:99-107.
Williams MT, Moran MS, Vorhees CV (2003) Refining the critical period for methamphetamine-induced spatial deficits in the Morris water maze. Psychopharmacology (Berl) 168:329-338.
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