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研究生: 江致遠
Chiang, Chih-yuan
論文名稱: 就解剖層面探究甲基安非他命成癮之相關記憶
Anatomical Substrates of the Methamphetamine Memory
指導教授: 游一龍
Yu, Lung
學位類別: 碩士
Master
系所名稱: 醫學院 - 行為醫學研究所
Institute of Behavioral Medicine
論文出版年: 2008
畢業學年度: 96
語文別: 英文
論文頁數: 30
中文關鍵詞: 前額葉記憶古典制約立即早期基因甲基安非他命
外文關鍵詞: Pavlovian conditioning, memory, methamphetamine, immediately early gene, prefrontal cortex
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  • 利用免疫染色的方式來偵測Fos蛋白質的表現及其活化情形,進而去標的特殊因應刺激而反應的神經元的方式,已被許多研究證實是可行且有效的。儘管我們已經知道甲基安非他命所引發的場地制約偏好反應是一個長期的記憶,但是我們對於此記憶在中樞神經系統是如何存放及提取,以及在哪裡存放和提取等都尚未明瞭。在本實驗中,我們以免疫染色的方式,偵測甲基安非他命所引發的場地制約偏好反應之記憶在提取後,邊緣系統中Fos蛋白質表現的變化。和以往的研究所不同的是,本實驗用以使動物提取記憶的方式並不是透過讓動物去表現該偏好記憶,而是將動物放至和當初甲基安非他命配對的類似環境中,利用這些環境線索的相似性來誘發其場地制約偏好反應之記憶。我們發現這樣的實驗設計可以有效地建立起場地制約偏好反應之表現及記憶,同時我們也發現當該記憶被提取時,在大腦內側前額葉皮質及伏隔核的核心部份Fos蛋白質的量都有顯著的上升情形。此外,我們也發現熟悉環境線索的刺激亦可造成大腦紋狀體背側以及齒狀迴的Fos蛋白質表現量上升。而伏隔核的外殼部份及杏仁核的側底核和側核部分,似乎並不參與在甲基安非他命引發的場地制約偏好反應之記憶的儲存和提取。綜合上述的結果,我們認為在邊緣系統中,內側前額葉皮質及伏隔核的核心部份參與在甲基安非他命引發的場地制約偏好反應之記憶的儲存和提取,而此兩個腦區為就解剖層面探討甲基安非他命成癮相關記憶之關鍵位置。

    Immunohistochemical Fos staining has proved to be a method to identify the loci of activated neurons specific to a stimulus. Although the methamphetamine (MA)-conditioned place preference (CPP) is a long-term memory, how and where the MA-CPP memory was stored and retrieved remained unknown. In this study, a conditioning procedure comprising of vehicle (saline) injection and previously-conditioned environment presentation, not performance test, was used as a way to reactivate the MA-CPP memory. Activated neurons in the limbic system following this MA-CPP memory reactivation were examined by employing immunohistochemical Fos staining. We demonstrated that the current conditioning procedure produced reliable MA-CPP memory and performance. Moreover, enhanced Fos expressions were obviously found in medial prefrontal cortex and the core of nucleus accumbens while the MA-CPP memory was reactivated. Different from many findings, familiarity with environmental cues/context in a novel surrounding (the CPP chamber) was found to significantly enhance neuronal activity in dorsal part of the striatum and the dentate gyrus. Nucleus accumbens shell, basolateral or lateral amygdala, in this regard, did not seem to be involved in the MA-CPP memory storage or retrieval. These results, taken together, suggest that medial prefrontal cortex and nucleus accumbens core are anatomical substrates responsible for storage and reactivation of the MA-conditioned cues/context-associated memory in the limbic system.

    Introduction----------------------------------------------------------------------------------------6-9 Materials and methods  Animals----------------------------------------------------------------------------------9-10  Drugs and Chemicals---------------------------------------------------------------------10  Conditioned place preference apparatus-------------------------------------------10-11  Experimental design------------------------------------------------------------------11-12  Immunohistochemical Staining for Fos Positive nuclei-------------------------12-13 Results  The 4-day conditioning protocol produced reliable MA-CPP memory and performance---------------------------------------------------------------------------13-14  MA-CPP memory reactivation enhanced FOS expression in medial prefrontal cortex and the core of nucleus accumbens--------------------------------------------14  Reactivation of memory associated with the commercial chambers enhanced FOS-positive nuclei in dorsal striatum and dentate gyrus-----------------------14-15  MA-CPP memory reactivation did not affect FOS expression in the shell of nucleus accumbens or amygdala--------------------------------------------------------15 Discussion---------------------------------------------------------------------------------------15-19 References---------------------------------------------------------------------------------------19-25 Figures  Figure 1-------------------------------------------------------------------------------------26  Figure 2-------------------------------------------------------------------------------------27  Figure 3-------------------------------------------------------------------------------------28  Figure 4---------------------------------------------------------------------------------29-30

    Adams, J.U., Careri, J.M., Efferen, T.R., & Rotrosen, J. (2000). Conditioned locomotor stimulant effects of cocaine in rats do not result from interference with habituation. Psychopharmacology, 151, 13-18.
    Anokhin, K.V., & Rose, S.P. (1991). Learning-induced increase of immediate early gene messenger RNA in the chick forebrain. European Journal of Neuroscience, 3, 162-167.
    Bernadi, R.E., Lattal, K.M., & Berger, S.P. (2006). Postretrieval propranolol disrupts a cocaine conditioned place preference. Neuroreport, 17, 1443-1447.
    Bossert, J.M., Busch, R.F., & Gray, S.M. (2005). The novel mGluR2/3 agonist LY379268 attenuates cue-induced reinstatement of heroin seeking. Neuroreport, 16, 1013-1016.
    Brody, A.L., Mandelkern, M.A., London, E.D., Childress, A.R., Lee, G.S., Bota, R.G., et al. (2002). Brain metabolic changes during cigarette craving. Archives of General Psychiatry, 59, 1162-1172.
    Brown, E.E., Robertson, G.S., & Fibiger, H.C. (1992). Evidence for conditional neuronal activation following exposure to a cocaine-paired environment: role of forebrain limbic structures. Journal of Neuroscience, 12, 4112-4121.
    Cherng, C.G., Tsai, C-W., Tsai, Y-P., Ho, M-C., Kao, S-F., & Yu, L. (2007). Methamphetamine-disrupted sensory procession mediates conditioned place preference performance. Behavioral Brain Research, 182, 103-108.
    Childress, A.R., Mozley, P.D., McElgin, W., Fitzgerald, J., Reivich, M., & O'Brien, C.P. (1999). Limbic activation during cue-induced cocaine craving. American Journal of Psychiatry, 156, 11-18.
    Chiu, R., Boyle, W.J., Meek, J., Smeal, T., Hunter, T., & Karin, M. (1988). The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell, 54, 541-542.
    Dravolina, O.A., Zakharova, E.S., Shekunova, E.V., Zvartau, E.E., Danysz, W., & Bespalov, A.Y. (2007). MGlu1 receptor blockade attenuates cue- and nicotine-induced reinstatement of extinguished nicotine self-administration behavior in rats. Neuropharmacology, 52, 263-269.
    Feltenstein, M.W., & See, R.E. (2006). Potentiation of cue-induced reinstatement of cocaine-seeking in rats by the anxiogenic drug yohimbine. Behavioral Brain Research, 174, 1-8.
    Feltenstein, M.W., & See, R.E. (2008). The neurocircuitry of addiction: an overview. British Journal of Pharmacology, 1-14, doi:10.1038/bjp.2008.51.
    Franklin, T.R., & Druhan, J.P. (2000). Expression of Fos-related antigens in the nucleus accumbens and associated regions following exposure to a cocaine-paired environment. European Journal of Neuroscience, 12, 2097-2106.
    Franklin, K.B.J., & Paxinos, G. (1997). The mouse brain in stereotaxic coordinates. Academic Press, San Diego, CA, USA.
    Greenberg, M.E., & Ziff, E.B. (1984). Stimulation of 3T3 cells induces transcription of the c-Fos proto-oncogene. Nature, 311, 433-438.
    Greenberg, M.E., Shyu, A.B., & Belasco, J.G. (1990). Deadenylyllation: a mechanism controlling c-Fos mRNA decay. Enzyme, 44, 181-192.
    Halazonetis, T.D., Georgopoulos, K., Greenberg, M.E., & Leder, P. (1988). c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities. Cell, 55, 917-924.
    Kaczmarek, L. (1993). Molecular biology of vertebrate learning: Is c-fos a new beginning? Journal of Neuroscience Research, 34, 377-381.
    Kaczmarek, L., & Nikolajew, E. (1990). c-fos protooncogene expression and neuronal plasticity. Acta Neurobiologiae Experimentalis, (Warsaw) 50, 173-179.
    Kamens, H., Burkhart-Kasch, S., McMinnon, C., Reed, C., & Phillips, T. (2005). Sensitivity to psychostimulants in mice bred for high and low stimulation to methamphetamine. Genes, Brain and Behavior, 4, 110-125.
    Kelamangalath, L., Swant, J., Stramiello, M., & Wagner, J.J. (2007). The effects of extinction training in reducing the reinstatement of drug-seeking behavior: involvement of NMDA receptors. Behavioral Brain Research, 185, 119-128.
    Kelley, J.B., Anderson, K.L., & Itzhak, Y. (2007). Long-term memory of cocaine-associated context: disruption and reinstatement. Neuroreport, 18, 777-780.
    Kouzarides, T., & Ziff, E. (1988). The role of the leucine zipper in the Fos-Jun interaction. Nature, 336, 646-651.
    Kovacs, K.J., & Sawchenko, P.E. (1996). Sequence of stress-induced alterations in indices of synaptic and transcriptional activation in parvocellular neurosecretory neurons. Journal of Neuroscience, 16, 262-273.
    Kuo, Y-M., Liang, K.C., Chen, H-H., Cherng, C.G., Lee, H-T., & Lin, Y., et al. (2007). Cocaine- but not methamphetamine-associated memory requires de novo protein synthesis. Neurobiology of Learning & Memory, 87, 93-100.
    LaLumiere, R.T., & Kalivas, P.W. (2008). Glutamate release in the nucleus accumbens core is necessary for heroin seeking. Journal of Neuroscience, 28, 3170-3177.
    Lee, J.L., Milton, A.L., & Everitt, B.J. (2006). Cue-induced cocaine seeking and relapse are reduced by disruption of drug memory reconsolidation. Journal of Neuroscience, 26, 5881-5887.
    Le Foll, B., Frances, H., Diaz, J., Schwartz, J.C., & Sokoloff, P. (2002). Role of the dopamine D3 receptor in reactivity to cocaine-associated cues in mice. European Journal of Neuroscience, 15, 2016-2026.
    Lien, W-H., Yeh, T-L., Yang, Y-K., Cherng, C.G., Chen, H-H., & Chen, P.S., et al. (2004). Cycloheximide enhances maintenance of methamphetamine-induced conditioned place preference. Chinese Journal of Physiology, 47, 23-30.
    Maleeva, N.E., Ivolgina, G.L., Anokhin, K.V., & Limborskaia, S.A. (1989). Analysis of the expression of the c-fos proto-oncogene in the rat cerebral cortex during learning. Genetika, 25, 1119-1121.
    Mead, A.N., Vasilaki, A., Spyraki, C., Duka, T., & Stephens, D.N. (1999). AMPA-receptor involvement in c-fos expression in the medial prefrontal cortex and amygdala dissociates neural substrates of conditioned activity and conditioned reward. European Journal of Neuroscience, 11, 4089-4098.
    Miller, C.A., & Marshall, J.F. (2004). Altered prelimbic cortex output during cue-elicited drug seeking. Journal of Neuroscience, 24, 6889-6897.
    Moffett, M.C., & Goeders, N.E. (2007). CP-154,526, a CRF type-1 receptor antagonist, attenuates the cue-and methamphetamine-induced reinstatement of extinguished methamphetamine-seeking behavior in rats. Psychopharmacology (Berlin), 190, 171-180.
    Morland, J., Jones, B.L., Palomares, M.L., & Alkana, R.L. (1994). Morphine-6-glucuronide: A potent stimulator of locomotor activity in mice. Life Sciences, 55, 163-168.
    Muller, R., Tremblay, J.M., Adamson, E.D., & Verma, I.M. (1983). Tissue and cell type-specific expression of two human c-oncogenes. Nature, 304, 454-456.
    Neisewander, J.L., Baker, D.A., Fuchs, R.A., Tran-Nguyen, L.T., Palmer, A., & Marshall, J.F. (2000). Fos protein expression and cocaine-seeking behavior in rats after exposure to a cocaine self-administration environment. Journal of Neuroscience, 20, 798-805.
    Panlilio, L.V., & Schindler, C.W. (1997). Conditioned locomotor-activating and reinforcing effects of discrete stimuli paired with intraperitoneal cocaine. Behavioral Pharmacology, 8, 691-698.
    Phillips, T.J., Huson, M., Gwiazdon, C., Burkhart-Kasch, S., & Shen, E.H. (1995). Effects of acute and repeated ethanol exposures on the locomotor activity of BXD recombinant inbred mice. Alcoholism, Clinical and Experimental Research, 19, 269-278.
    Reijmers, L.G., Perkins, B.L., Matsuo, N., & Mayford, M. (2007). Localization of a stable neural correlate of associative memory. Science, 317, 230-233.
    Rogers, J.L., & See, R.E. (2007). Selective inactivation of the ventral hippocampus attenuates cue-induced and cocaine-primed reinstatement of drug-seeking in rats. Neurobiology of Learning & Memory, 87, 688-692.
    Schroeder, B.E., Binzak, J.M., & Kelley, A.E. (2001). A common profile of prefrontal cortical activation following exposure to nicotine- or chocolate-associated contextual cues. Neuroscience, 105, 535-545.
    Schroeder, B.E., Holahan, M.R., Landry, C.F., & Kelley, A.E., (2000), Morphine-associated environmental cues elicit conditioned gene expression. Synapse, 37, 146-158.
    Swank, M.W., Ellis, A.E., & Cochran, B.N. (1996). c-Fos antisense blocks acquisition and extinction of conditioned taste aversion in mice. NeuroReport, 7, 1866-1870.
    Thiriet, N., Zwiller, J., & Ali, S.F. (2001). Induction of the immediate early genes egr-1 and c-Fos by methamphetamine in mouse brain. Brain Research, 919, 31-40.
    Tischmeyer, W., Kaczmarek, L., Strauss, M., Jork, R., & Matthies, H. (1990). Accumulation of c-fos mRNA in rat hippocampus during acquisition of a brightness discrimination. Behavioral and Neural Biology, 54, 165-171.
    Tolliver, B.K., & Carney, J.M. (1995). Locomotor stimulant effects of cocaine and novel cocaine analogs in DBA/2J and C57BL/6J inbred mice. Pharmacology, Biochemistry and Behavior, 50, 163-169.
    Topple, A.N., Hunt, G.E., & McGregor, I.S. (1998). Possible neural substrates of beer-craving in rats. Neuroscience Letter, 252, 99-102.
    Ventura, R., Alcaro, A., & Puglisi-Allegra, S. (2005). Prefrontal cortical norepinephrine release is critical for morphine-induced reward, reinstatement and dopamine release in the nucleus accumbens. Cerebral Cortex, 15, 1877-1886.
    Vosatka, R.J., Hermanowski-Vosatka, A., Metz, R., & Ziff, E.B. (1989). Dynamic interactions of c-Fos protein in serum-stimulated 3T3 cells. Journal of Cell Physiology, 138, 493-502.
    Yan, Y., Yamada, K., Nitta, A., & Nabeshima, T. (2007). Transient drug-primed but persistent cue-induced reinstatement of extinguished methamphetamine-seeking behavior in mice. Behavioral Brain Research, 177, 261-268.
    Zavala, A.R., Osredkar, T., Joyce, J.N., & Neisewander, J.L. (2008). Upregulation of Ark mRNA expression in the prefrontal cortex following cue-induced reinstatement of extinguished cocaine-seeking behavior. Synapse, 62, 421-431.
    Zhao, Y., Dayas, C.V., Aujla, H., Baptista, M.A., Martin-Fardon, R., & Weiss, F. (2006). Activation of group II metabotropic glutamate receptors attenuates both stress and cue-induced ethanol-seeking and modulates c-fos expression in the hippocampus and amygdala. Journal of Neuroscience, 26, 9967-9974.
    Zhao, S., Pang, Y., Beuerman, R.W., Thompson, H.W., & Kline, D.G. (1998). Expression of c-Fos protein in the spinal cord after brachial plexus injury: comparison of root avulsion and distal nerve transection. Neurosurgery, 42, 1357-1362.

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