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Reevaluation of the Anhedonia Hypothesis of Dopamine Blocking

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Reevaluation of the Anhedonia Hypothesis of Dopamine Blocking 國立中正大學心理學研究所博士論文 Haloperidol 干擾正向與負向味覺刺激的反應：多巴胺阻斷 劑的”Anhedonia”假設之檢視 Haloperidol interferes with the impact of rewarding and aversive stimuli: Re-appraisal of the anhedonia hypothesis of dopamine blocking 研究生 黃智偉 撰 指導教授 蕭世朗 博士 中華民國 九十二 年 七 月 Haloperidol Interferes with the impact of Rewarding and aversive Stimuli: Reappraisal of the Anhedonia Hypothesis of Dopamine Blocking by Andrew Chih Wei Huang Department of Psychology National Chung Cheng University 160 San-Hsing, Min-Hsiung, Chia-Yi 621, Taiwan, R.O.C. A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy July, 2003 ii Abstract The present study examined that a non-selective D2 receptor antagonist, haloperidol, attenuated the US regardless of rewarding and aversive stimuli on the conditioned taste aversion and taste solution intake paradigms. It was shown that the brain DA system mediated the impact of aversive or rewarding US, and revised the preceding anhedonia hypothesis of DA blocking in general without the valence of stimulus. Besides, the salient stimuli hypothesis of brain DA is to substitute the anhedonia hypothesis. However, the data indicated that so-called salient stimuli did not mean the taste unfamiliarity (novelty). Rather, it is probable the reinforcing effect of stimuli. Taken together, brain DA system probably plays a crucial role to implicate the reinforcing effect of stimuli. However, whether a stimulus has a reinforcing value seems to depend on the animals’ condition, except few primary reinforcers. After the investigation, some new issues emerge, and need to investigate in the future. iii 摘要 本研究使用味覺嫌惡制約及味覺溶液攝食的動物行為模式，檢驗 多巴胺阻斷劑 haloperidol 是否能削弱正向及負向未制約刺激的效 果。結果顯示腦內多巴胺系統不僅牽涉正向未制約刺激也影響負向未 制約刺激，此結果修正早期多巴胺 anhedonia 的假設，支持最近的 腦內多巴胺牽涉 salient stimuli 的新假設，並且對該假設提出更 進一步的釐清，認為所謂的 salient stimuli很可能指的不是刺激的 新奇性(novelty)，而是刺激的酬賞特性，而腦內多巴胺系統可能負 責此一功能。然而刺激是否具有酬賞效果，也可能會隨動物的內外環 境的狀態而改變。許多關於腦內多巴胺系統功能的新問題及新議題在 本研究裏發現，仍待之後的研究釐清。 iv Table of Contents Abstract -------------------------------------------------------------------------------------ii Chapter 1. -----------------------------------------------------------------------------------1. Introduction ---------------------------------------------------------------------------1. The discovery of the neural substrate of positive reinforcement --------1. The anhedonia hypothesis of dopamine (DA) ------------------------------1. Challenges to the anhedonia hypothesis of DA blocking -----------------5. Critique 1. ------------------------------------------------------------------------5. Critique 2. ------------------------------------------------------------------------6. Critique 3. ------------------------------------------------------------------------7. Opposite evidence --------------------------------------------------------------10. Sensory processing function of brain DA neurons -------------------------12. The involvement of amygdala to aversive and rewarding stimulus associations ----------------------------------------------------------------------13. Neuroanatomical and behavioral data ----------------------------------------15. The present investigation -------------------------------------------------------17. Chapter 2. -------------------------------------------------------------------------------------19. General Method ------------------------------------------------------------------------19. Chapter 3. -------------------------------------------------------------------------------------22. v Experiment 1A -------------------------------------------------------------------------22. Experiment 1B -------------------------------------------------------------------------27. Experiment 2A --------------------------------------------------------------------------30. Experiment 2B --------------------------------------------------------------------------33. Discussion --------------------------------------------------------------------------------35. Chapter 4. --------------------------------------------------------------------------------------39. Experiment 3 -----------------------------------------------------------------------------40. Discussion --------------------------------------------------------------------------------51. Chapter 5. --------------------------------------------------------------------------------------52. Experiment 4 ----------------------------------------------------------------------------53. Discussion --------------------------------------------------------------------------------60. Chapter 6. --------------------------------------------------------------------------------------63. Experiment 5 -----------------------------------------------------------------------------63. Experiment 6 -----------------------------------------------------------------------------66. Discussion --------------------------------------------------------------------------------69. Chapter 7. --------------------------------------------------------------------------------------71. Experiment 7 -----------------------------------------------------------------------------74. Experiment 8 -----------------------------------------------------------------------------83. Discussion --------------------------------------------------------------------------------92. vi Chapter 8. --------------------------------------------------------------------------------------96. General Discussion ---------------------------------------------------------------------96. Against the viewpoint of motor impairment ----------------------------------98. What is a salient stimulus? ------------------------------------------------------98. Arguments and Issues -----------------------------------------------------------101. 1. Confirmation of HAL Effect ------------------------------------------101. 2. High sucrose is not attenuated by HAL ------------------------------102. 3. Relativity of Reinforcement -------------------------------------------103. 4. A Probable Cause Regards to Generate Animals’ Approaching and Avoiding Behaviors ---------------------------------------------------105. Conclusion ------------------------------------------------------------------------------106. References ------------------------------------------------------------------------------------107. vii List of Figures 1 -----------------------------------------------------------------------------------------------26. 2 -----------------------------------------------------------------------------------------------29. 3 -----------------------------------------------------------------------------------------------32. 4 -----------------------------------------------------------------------------------------------34. 5 -----------------------------------------------------------------------------------------------42. 6 -----------------------------------------------------------------------------------------------44. 7 -----------------------------------------------------------------------------------------------46. 8 -----------------------------------------------------------------------------------------------48. 9 -----------------------------------------------------------------------------------------------50. 10 ----------------------------------------------------------------------------------------------56. 11 ----------------------------------------------------------------------------------------------57. 12 ----------------------------------------------------------------------------------------------58. 13 ----------------------------------------------------------------------------------------------59. 14 ----------------------------------------------------------------------------------------------65. 15 ----------------------------------------------------------------------------------------------68. 16 ----------------------------------------------------------------------------------------------75. 17 ----------------------------------------------------------------------------------------------76. 18 ----------------------------------------------------------------------------------------------78. viii 19 -----------------------------------------------------------------------------------------------80. 20 -----------------------------------------------------------------------------------------------82. 21 -----------------------------------------------------------------------------------------------84. 22 -----------------------------------------------------------------------------------------------85. 23 -----------------------------------------------------------------------------------------------87. 24 -----------------------------------------------------------------------------------------------89. 25 -----------------------------------------------------------------------------------------------91. ix Appendix 1. Histological Verification: Central nucleus of amygdala ID No target Unilateral target Bilateral target Left Right 1g1 ＊ 2g1 ＊ 3g1 ＊ 4g1 ＊ 5g1 ＊ 6g1 ＊ 7g1 ＊ 8g1 ＊ 1g2 ＊ 2g2 ＊ 3g2 ＊ 4g2 ＊ 5g2 ＊ 6g2 ＊ 7g2 ＊ 8g2 ＊ Note: g1 represents the group that was given vehicle prior to NaCl, whereas g2 was injected HAL before NaCl. Besides, one week later, the same rats received the identical drug treatment and then LiCl test. 「＊」 indicates the condition of injected location. x Appendix 2. Histological Verification: Central nucleus of amygdala ID No target Unilateral target Bilateral target Left Right 1g3 ＊ 2g3 ＊ 3g3 ＊ 4g3 ＊ 5g3 ＊ 6g3 ＊ 7g3
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