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https://ah.lib.nccu.edu.tw/handle/140.119/54867| 題名: | 電刺激大鼠側韁核對區辨性低頻操作式制約行為的影響 The effects of electrical stimulation in the lateral habenula on operant behavior maintained by the differential reinforcement of low-rate (DRL) schedule of reinforcement in the rat |
作者: | 林禧岳 | 貢獻者: | 廖瑞銘 林禧岳 |
關鍵詞: | 深部大腦電刺激 區辨性低頻操作式制約(DRL)行為 側韁核 多巴胺受體抑制劑 正腎上腺素受體抑制劑 deep brain stimulation differential reinforcement of low-rate responding behavior lateral habenula dopamine receptor antagonists norepinephrine receptor antagonists |
日期: | 2011 | 上傳時間: | 30-Oct-2012 | 摘要: | 透過神經科學的研究，對於大腦的行為功能已有一定的認識，不同於以往的認識，目前認為神經行為機制不只由單一腦區或單一神經化學系統所調控。深部大腦電刺激經常被用來研究特定腦區的行為功能。但是，深部大腦電刺激的作用機制仍然不清楚。最近幾年臨床研究發現，利用電刺激在側韁核成功的治療憂鬱症患者。然而，目前認為側韁核與多巴胺系統互為負回饋作用，共同參與在動機行為的酬賞反應中。本實驗室先前的研究顯示，破壞韁核造成區辨性低頻操作式制約行為 (簡稱DRL行為)學習的障礙，然而，電刺激在側韁核造成DRL行為表現的結果還是未知的。所以，本實驗主要以電刺激在側韁核觀察大鼠行為上的改變，探討側韁核在行為上參與的功能。實驗一的結果顯示電刺激在側韁核並不影響自發性運動能力，在不同電流強度的刺激下也不會影響。實驗二的結果顯示電刺激在側韁核造成DRL 15秒的行為有類安非他命效果之行為表現，在高頻率電刺激有較顯著類安非他命的效果。實驗三的結果顯示電刺激在側韁核造成DRL 15秒的行為之影響，會被多巴胺受體抑制劑所抵消，而單獨注射巴胺受體抑制劑並不影響DRL 15秒的行為。實驗四的結果顯示電刺激在側韁核造成DRL 15秒的行為之影響，不會被正腎上腺素受體抑制劑所抵消。實驗五的結果顯示電刺激在側韁核造成DRL 72秒的行為之影響並不如DRL 15秒的行為顯著。實驗六的結果顯示電刺激在側韁核並不會造成大鼠無法區辨酬賞的量。綜合而言，側韁核在動機行為的角色，是透過影響多巴胺系統造成行為的改變。 Behavioral function of the brain has been studied in neuroscience and progressively accumulated informative data to reveal the neurobehavioral mechanisms. It is now realized that those underlying mechanisms of behaviors is not as such simple as previous thought of limiting only in one locus of the brain or solely by one neurochemical system. The deep brain stimulation is usually used to study the behavioral function of specific brain regions. However, the mechanism of the deep brain stimulation is still unclear. The previous study has shown that electrical stimulation of the lateral habenula (LHb) successfully treated depression symptoms in the patients. It is proposed that an inhibitory role of LHb on the mibrain dopamine (DA) system which mediates the reward-related behavior. A previous study of this lab showed that lesion of habenula impaired the acquisition of differential reinforcement of low-rate responding (DRL) behavior. But, the effect of LHb stimulation on the DRL behavior is still unclear. To determine the functions of LHb involving in the behavior, the electrical stimulation was applied in LHb to observe the behavioral change of rats. The results of Experiment 1 showed that the LHb stimulation had no effect on locomotor activity. In Experiment 2, the LHb stimulation was shown to affect DRL 15-s behavior, which effects were similar to those affected by amphetamine. Experiment 3 showed that the DA receptor antagonists reversed the effects of LHb stimulation, while experiment 4 showed that norepinephrine (NE) receptor antagonists had no reversal effect on DRL 15-s behavior. In Experiment 5, the amphetamine-like behavior induced by LHb stimulation had subtle effects on DRL 72-s behavior. Experiment 6 showed that the LHb stimulation had no effect on a discrimination task. These data suggest that the LHb modulating DRL behavior is DA-dependent. |
參考文獻: | References\nAndrade, D., Zumsteg, D., Hamani, C., Hodaie, M., Sarkissian, S., Lozano, A. & Wennberg, R. (2006) Long-term follow-up of patients with thalamic deep brain stimulation for epilepsy. Neurology, 66:1571-1573.\nBromberg-Martin, E.S., Matsumoto, M., Nakahara, H. & Hikosaka, O. (2010a) Multiple timescales of memory in lateral habenula and dopamine neurons. Neuron, 67:499-510.\nBromberg-Martin, E.S., Matsumoto, M. & Hikosaka, O. (2010b) Dopamine in motivational control: rewarding, aversive, and alerting. Neuron, 68:815-834.\nCheng, RK & Liao, RM (2007) Dopamine receptor antagonists reverse amphetamine-induced behavioral alteration on a differential reinforcement for low-rate (DRL) operant task in the rat. Chin J Physiol, 50:77-88.\nChiang, F-K (2006) Function of the habenula measured by operant conditioned behavior based on temporal contingency. An unpublished master thesis in National Cheng-Chi University, Taipei. \nCole, S.O. (1978) Brain mechanisms of amphetamine-induced anorexia, locomotion, and stereotypy: A review. Neurosci Biobehav Rev, 2:89-100.\nFeuerstein, T.J., Kammerer, M., Lücking, C.H. & Moser, A. (2011) Selective GABA release as a mechanistic basis of high-frequency stimulation used for the treatment of neuropsychiatric diseases. Naunyn-Schmiedebergs Arch Pharmacol, 1-20.\nFriedman, A., Lax, E., Dikshtein, Y., Abraham, L., Flaumenhaft, Y., Sudai, E., Ben-Tzion, M., Ami-Ad, L., Yaka, R. & Yadid, G. (2010) Electrical stimulation of the lateral habenula produces enduring inhibitory effect on cocaine seeking behavior. Neuropharmacology, 59:452-459.\nFriedman, A., Lax, E., Dikshtein, Y., Abraham, L., Flaumenhaft, Y., Sudai, E., Ben-Tzion, M. & Yadid, G. (2011) Electrical stimulation of the lateral habenula produces an inhibitory effect on sucrose self-administration. Neuropharmacology, 60:381-387.\nGeisler, S. & Trimble, M. (2008) The lateral habenula: no longer neglected. CNS Spectr, 13:484-489.\nGhods-Sharifi, S., Onge, J.R.S. & Floresco, S.B. (2009) Fundamental contribution by the basolateral amygdala to different forms of decision making. J Neurosci, 29:5251-5259.\nGifuni, A.J., Jozaghi, S., Gauthier-Lamer, A.C. & Boye, S.M. (2012) Lesions of the lateral habenula dissociate the reward-enhancing and locomotor-stimulant effects of amphetamine. Neuropharmacology.\nGross, R.E. & Lozano, A.M. (2000) Advances in neurostimulation for movement disorders. Neurol Res, 22:247-258.\nGutman, D.A., Holtzheimer, P.E., Behrens, T.E.J., Johansen-Berg, H. & Mayberg, H.S. (2009) A tractography analysis of two deep brain stimulation white matter targets for depression. Biol Psychiatry, 65:276-282.\nHikosaka, O., Sesack, S.R., Lecourtier, L. & Shepard, P.D. (2008) Habenula: crossroad between the basal ganglia and the limbic system. J Neurosci, 28:11825-11829.\nHiller, A., Loeffler, S., Haupt, C., Litza, M., Hofmann, U. & Moser, A. (2007) Electrical high frequency stimulation of the caudate nucleus induces local GABA outflow in freely moving rats. J Neurosci Methods, 159:286-290.\nJahanshahi, M., Ardouin, C., Brown, R., Rothwell, J., Obeso, J., Albanese, A., Rodriguez-Oroz, M., Moro, E., Benabid, A. & Pollak, P. (2000) The impact of deep brain stimulation on executive function in Parkinson`s disease. Brain, 123:1142-1154.\nJi, H. & Shepard, P.D. (2007) Lateral habenula stimulation inhibits rat midbrain dopamine neurons through a GABAA receptor-mediated mechanism. J Neurosci, 27:6923-6930.\nJiménez, F., Velasco, F., Salin-Pascual, R., Hernández, J.A., Velasco, M., Criales, J.L. & Nicolini, H. (2005) A patient with a resistant major depression disorder treated with deep brain stimulation in the inferior thalamic peduncle. Neurosurgery, 57:585-593.\nKim, U. (2009) Topographic commissural and descending projections of the habenula in the rat. J Comp Neurol, 513:173-187.\nLecourtier, L. & Kelly, P.H. (2007) A conductor hidden in the orchestra? Role of the habenular complex in monoamine transmission and cognition. Neurosci Biobehav Rev, 31:658-672.\nLecourtier, L., DeFrancesco, A. & Moghaddam, B. (2008) Differential tonic influence of lateral habenula on prefrontal cortex and nucleus accumbens dopamine release. Eur J Neurosci, 27:1755-1762.\nLee, K.H., Kristic, K., van Hoff, R., Hitti, F.L., Blaha, C., Harris, B., Roberts, D.W. & Leiter, J. (2007) High-frequency stimulation of the subthalamic nucleus increases glutamate in the subthalamic nucleus of rats as demonstrated by in vivo enzyme-linked glutamate sensor. Brain Res, 1162:121-129.\nLi, B., Piriz, J., Mirrione, M., Chung, C.H., Proulx, C.D., Schulz, D., Henn, F. & Malinow, R. (2011) Synaptic potentiation onto habenula neurons in the learned helplessness model of depression. Nature, 470:535-539.\nLi, T.L., Qadri, F. & Moser, A. (2004) Neuronal electrical high frequency stimulation modulates presynaptic GABAergic physiology. Neurosci Lett, 371:117-121.\nLiao, R. & Cheng, R. (2005) Acute effects of d-amphetamine on the differential reinforcement of low-rate (DRL) schedule behavior in the rat: comparison with selective dopamine receptor antagonists. Chin J Physiol, 48:41-50.\nLiao, R.M. (2009) Effects of Amphetamine and Cocaine on Behavior Maintained by Differential Reinforcement of Low-Rate-Response (DRL) Schedule. Chin J Physiol, 52:250-263.\nMeng, H., Wang, Y., Huang, M., Lin, W., Wang, S. & Zhang, B. (2011) Chronic deep brain stimulation of the lateral habenula nucleus in a rat model of depression. Brain Res, 1422:32-38.\nMaciunas, R.J., Maddux, B.N., Riley, D.E., Whitney, C.M., Schoenberg, M.R., Ogrocki, P.J., Albert, J.M. & Gould, D.J. (2007) Prospective randomized double-blind trial of bilateral thalamic deep brain stimulation in adults with Tourette syndrome. J Neurosurg, 107:1004-1014.\nMatsumoto, M. & Hikosaka, O. (2007) Lateral habenula as a source of negative reward signals in dopamine neurons. Nature, 447:1111-1115.\nMatsumoto, M. & Hikosaka, O. (2008) Representation of negative motivational value in the primate lateral habenula. Nat Neurosci, 12:77-84.\nMayberg, H.S., Lozano, A.M., Voon, V., McNeely, H.E., Seminowicz, D., Hamani, C., Schwalb, J.M. & Kennedy, S.H. (2005) Deep brain stimulation for treatment-resistant depression. Neuron, 45:651-660.\nMorissette, M.C. & Boye, S.M. (2008) Electrolytic lesions of the habenula attenuate brain stimulation reward. Behav Brain Res, 187:17-26.\nO’Donnell JM, Marek GJ, Seiden LS (2005) Antidepressant effects assessed using behavior maintained under a differential-reinforcement-of-low-rate (DRL) operant schedule. Neurosci Behav Rev, 29:785-798\nOkamoto, L.E., Shibao, C., Gamboa, A., Choi, L., Diedrich, A., Raj, S.R., Black, B.K., Robertson, D. & Biaggioni, I. (2012) Synergistic Effect of Norepinephrine Transporter Blockade and α-2 Antagonism on Blood Pressure in Autonomic Failure. Hypertension, 59:650-656.\nPerozzo, P., Rizzone, M., Bergamasco, B., Castelli, L., Lanotte, M., Tavella, A., Torre, E. & Lopiano, L. (2001) Deep brain stimulation of the subthalamic nucleus in Parkinson`s disease: comparison of pre-and postoperative neuropsychological evaluation. J Neurol Sci, 192:9-15.\nRichardson, D.W., Freund, J., Gear, A.S., Mauck, H. & Preston, L.W. (1968) Effect of propranolol on elevated arterial blood pressure. Circulation, 37:534-542.\nSartorius, A. & Henn, F.A. (2007) Deep brain stimulation of the lateral habenula in treatment resistant major depression. Med Hypotheses, 69:1305-1308.\nSanger, DJ & Blackman, DE (1989) Operant behavior and the effects of centrally acting drugs. In: Neuromethods: Psychopharmacology (Boulton, A. A., Baker, G. B. and Greenshaw, A. J. Clifton, ed), vol.13, pp. 299-348. New Jersey: Humana Press.\nSchlaepfer, T., Frick, C., Zobel, A., Maier, W., Heuser, I., Bajbouj, M., O`Keane, V., Corcoran, C., Adolfsson, R. & Trimble, M. (2008) Vagus nerve stimulation for depression: efficacy and safety in a European study. Psychol Med, 38:651-662.\nSchumacher, A., Vasconcelos, A.P., Lecourtier, L., Moser, A. & Cassel, J.C. (2011) Electrical high frequency stimulation in the dorsal striatum: Effects on response learning and on GABA levels in rats. Behav Brain Res. 222:368-374.\nShumake, J., Ilango, A., Scheich, H., Wetzel, W. & Ohl, F.W. (2010) Differential neuromodulation of acquisition and retrieval of avoidance learning by the lateral habenula and ventral tegmental area. J Neurosci, 30:5876-5883.\nSkinner, BF (1938) The Behavior of Organisms. New York, New York: Appleton Century Crofts.\nSt. Onge, J.R., Chiu, Y.C. & Floresco, S.B. (2010) Differential effects of dopaminergic manipulations on risky choice. Psychopharmacology, 211:209-221.\nSutherland, RJ (1982) The dorsal diencephalic conduction system: a review of the anatomy and functions of the habenular complex. Neurosci Biobehav Rev, 6,:1-13.\nTemel, Y., Boothman, L.J., Blokland, A., Magill, P.J., Steinbusch, H.W.M., Visser-Vandewalle, V. & Sharp, T. (2007) Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-frequency stimulation of the subthalamic nucleus. Proc Natl Acad Sci, 104:17087-17092.\nVachon, M.P. & Miliaressis, E. (1992) Dorsal diencephalic self-stimulation: A movable electrode mapping study. Behav Neurosci, 106:981-991.\nVelasco, F., Velasco, M., Jiménez, F., Velasco, A.L. & Salin-Pascual, R. (2005) Neurobiological background for performing surgical intervention in the inferior thalamic peduncle for treatment of major depression disorders. Neurosurgery, 57:439-448.\nWang, Y., Zhang, F., Tang, S., Lai, M., Hao, W., Zhang, Y., Yang, J. & Zhou, W. (2009) Lack of effect of habenula lesion on heroin self-administration in rats. Neurosci Lett, 461:167-171.\nWichmann, T. & DeLong, M.R. (2006) Deep brain stimulation for neurologic and neuropsychiatric disorders. Neuron, 52:197-204. | 描述: | 碩士 國立政治大學 神經科學研究所 99754001 100 |
資料來源: | http://thesis.lib.nccu.edu.tw/record/#G0099754001 | 資料類型: | thesis |
| Appears in Collections: | 學位論文 |
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