臺灣博碩士論文加值系統

　　對於由成癮性藥物所造成嫌惡效果的味覺嫌惡制約，是一種令人感到有趣的現象，但是對於這種現象形成的原因卻是令人不解，目前主要的假設是酬償比較假說，認為飲量抑制效果是酬償比較所產生的，但仍有許多的研究並不支持這個假說，近年來的研究，多是利用味覺嫌惡制約（Condition taste aversion,CTA）和區域偏好制約（Condition place preference,CPP）來比較兩者是否涉及相同的學習機制，但這些研究大多只是行為上的比較，而較少直接對大腦神經迴路進行確認，所以本研究希望從神經機制的角度，來檢証酬償比較假說的正確性。
　　在之前的研究發現，對於味覺嫌惡制約和區域偏好制約的比較來檢証酬償比較假說的研究多停留在行為階段，較沒有神經機制方面的研究，所以實驗一希望使用神經機制方面的研究來探討味覺嫌惡制約和區域偏好制約兩種實驗典範的差異，進而檢証酬賞比較假說的正確性。實驗二則是在確定大白鼠體內可體松含量的變化，是與飲量抑制效果有關，或是與味覺嫌惡制約的效果有關，進一步推測大白鼠產生壓力的來源，來檢証酬償比較假說。
　　在本研究中各有支持酬償比較假說與單純制約假說的結果，這說明了這兩個假說不完全對，各有部分可以解釋成癮性藥物誘導的味覺嫌惡制約現象的假設，但在分歧的結果上也說明其內容各有不完整的地方，希望在未來能有更多的研究結果來發展出新的假說。

摘要‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧i
目錄‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧ii
圖目‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧iii
緒論‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧01
一、 文獻回顧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧01
二、 實驗目的‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧05
材料與方法‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧06
一、 受試者‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧06
二、 藥品‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧06
三、 埋管手術‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧06
四、 顱內藥物注射‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧07
五、 實驗儀器及步驟‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧07
六、 取血與檢驗可體松‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧08
七、 組織切片‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧10
八、 分析方法‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧10
實驗設計‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧11
結果‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧13
討論‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧16
參考文獻‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧21

圖一 不同組別在區域偏好制約上的表現‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧25
圖二 破壞VTA後的飲量變化‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧26
圖三 破壞PAG後的飲量變化‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧27
圖四 制約3次各種不同藥物制約的飲量變化‧‧‧‧‧‧‧‧‧‧‧‧‧28
圖五 制約6次各種不同藥物制約的飲量變化‧‧‧‧‧‧‧‧‧‧‧‧‧29
圖六 制約12次各種不同藥物制約的飲量變化‧‧‧‧‧‧‧‧‧‧‧‧‧30
圖七 表示不同制約次數間各種藥物的可體松的變化百分比‧‧‧‧‧‧‧31
圖八 不同藥物間的可體松濃度變化百分比‧‧‧‧‧‧‧‧‧‧‧‧‧‧32
圖九 表示不同制約次數間各種藥物的腎上腺重量的變化‧‧‧‧‧‧‧‧33
圖十 不同藥物間的腎上腺重量變化‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧34
圖十一 VTA埋管位置‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧35
圖十二 PAG埋管位置‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧‧36

Branda˜o M.L., Anseloni V.Z., Pando´ssio J.E., Arau´jo J.E. De, Castilho V.M.. Neurochemical mechanisms of the defensive behavior in the dorsal midbrain. Neuroscience and Biobehavioral Reviews(1999), 23, 863–875.
Carobrez Antonio P.,Teixeira Karina V., Graeff Frederico G..Moudulation of defensive behavior by Periaqueductal gray NMDA/glycine-B receptor. Ncuroscience and Biobehavioral Reviews(2001), 25, 697-709.
Clark J. J., Bernstein I. L.. Reciprocal cross-sensitization between amphetamine and salt appetite. Pharmacology, Biochemistry and Behavior 78 (2004), 691–698
Di, S. G., Mana, M. J., Jacobs, W. J.,& Phillips, A. G.Evidence of Pavlovion conditioned fear following electrical stimulation of the periaqueductal gray in the rat. Physiol Behave.(1987), 40(1), 55-63.
Glowa J. R., Shaw Amy E., Riley Anthony L.. Cocaine-induced conditioned taste aversions: comparisons between effects in LEW/N and F344/N rat strains. Psychopharmacology (1994), 114:229-232.
Gomez Felipe, Leo Nicole A., Grigson P. S.. Morphine-induced suppression of saccharin intake is correlated with elevated corticosterone levels. Brain Research(2000) . 863, 52–58.
Gomez F., Grigson P. S.. The suppressive effects of LiCl, sucrose, and
drugs of abuse are modulated by sucrose concentration in food-deprived rats. Physiology & Behavior(1999) .Vol67 ,No.3 ,351–357.
Grigson P. S.. Conditioned Taste Aversions and Drugs of Abuse: A Reinterpretation. Behavioral Ncuroscience(1997), Vol. Ill,No. 1,129-136.
Grigson P. S., Lyuboslavsky Polina, Tanase Diana. Bilateral lesions of the gustatory thalamus disrupt morphine- but not LiCl-induced intake suppression in rats: evidence against the conditioned taste aversion hypothesis. Brain Research(2000), 858,327–337.
Andrew Huang, Sigmund Hsiao . Re-examination of Amphetamine-Induced Conditioned Suppression of Tastant Intake in Rats: The Task-Dependent Drug Effects Hypothesis. Behavioral Neuroscience(2008), Vol. 122, No. 6, 1207–1216.
Kent W. D. T., Cross-Moller S. K. & Ossenkopp K. P. Acute effect of corticosterone on LiCl-induced rapid gustatory condictioning in rats: a microstructural analysis of licking patterns. Behavioral Brain Research(2002), 136, 143-150.
Koob, G. F.,& Swerdlow, N. R.. The functional output of the mesolimbic dopamine system. Annal of New York Academy of Science(1988), 537, 216-227.
Lett BT, Grant VL.. Conditioned taste preference produced by pairing a taste with a low dose of morphine or sufentanil. Psychopharmacology(1989), 98(2), 236-9.
Linda A. Parker. Taste Reactivity Responses Elicited by Reinforcing
Drugs: A Dose-Response Analysis. Behavioral Neuroscience(1991), 98(2), 236-9.
Oades, R. D.,& Halliday, G. M.. Ventral tegmental(A10) system：neurobiology. 1.Anatomy and connectivity. Brain Res(1987), 434(2), 117-165.
Miroslav Adzic, Jelena Djordjevic, Ana Djordjevic, Ana Niciforovic, Constantinos Demonacos, Marija Radojcic, and Marija Krstic-Demonacos. Acute or chronic stress induce cell compartment-specific phosphorylation of glucocorticoid receptor and alter its transcriptional activity in Wistar rat brain. J Endocrinol(2009), 202(1): 87–97.
Paul J. Fletcher, Catherine C. Tenn, Zoë Rizos, Vedran Lovic, Shitij Kapur. Sensitization to amphetamine,but not PCP,impairs attentional set shifting:reversal by a D1 receptor agonist injected into the medial prefrontal cortex. Psychopharmacology (2005), 183, 190–200.
R. Pedroza-Llinas, L. Ramirez-Lugo, K. Guzman-Ramos, S. Zavala-Vega, F. Bermudez-Rattoni. Safe taste memory consolidation is disrupted by a protein synthesis inhibitor in the nucleus accumbens shell. Neurobiology of Learning and Memory(2009),
Simpson Gregory R., Riley Anthony L.. Morphine preexposure facilitates morphine place preference and attenuates morphine taste aversion. Pharmacology, Biochemistry and Behavior(2005), 80, 471–479.
Tsigos Constantine, Chrouso George P.. Hypothalamic–pituitary–adrenal axis, neuroendocrine factors and stress. Journal of Psychosomatic Research(2002), 53, 865– 871.
Ying-Chou Wang, Andrew Chih Wei Huang, Sigmund Hsiao. Paradoxical simultaneous occurrence of amphetamine-induced conditioned taste aversion and conditioned place preference with the same single drug injection:A new“pre- and post-association”experimental paradigm. Pharmacology, Biochemistry and Behavior(2010),