雖然焦慮是一種普遍存在之情感性心智活動，迄今仍無充份解釋之實證資料。本研究主要是利用一種焦慮症相關的動物模式，即抬高式T形迷津，探討與焦慮症有關的神經行為機制。整部研究分兩大實驗，分別探討抬高式T形迷津的行為建構動力與破壞依核次級區域在抬高式T形迷津或其他焦慮作業上之行為表現。在實驗一檢驗抬高式T形迷津的行為內涵方面，共有四個實驗：實驗一A探討抬高式T形迷津抑制性躲避行為是否呈現消除現象；實驗一B探討破壞制約害怕神經網路對抬高式T形迷津之抑制性躲避行為的影響，並檢測自發性運動量的改變是否造成干擾效果；實驗一C探討事前暴露經驗對脫逃行為的意義；實驗一D檢測脫逃及抑制性躲避實驗程序互相干擾之可能性。實驗二探討可能涉及抬高式T形迷津或其他焦慮作業的神經機制，針對破壞依核次級區域對焦慮行為的影響進行檢測。此部分包含三個實驗，實驗二A探討依核次級區域受損對傳統焦慮動物模式抬高式十字迷津行為的影響；實驗二B採用已在實驗一建立行為效度的抬高式T形迷津，檢驗破壞依核次級區域後的迷津行為表現，並檢驗依核次級區域受損是否影響受試自發性運動量變化，以致干擾抬高式T形迷津的行為表現。另為深入探討依核的功能角色，實驗二C利用其他嫌惡作業測試破壞依核次級區域對制約躲避電擊行為的影響。實驗一結果顯示抑制性躲避行為是一包含制約害怕及探索行為等多重歷程的行為模式，而脫逃行為對情緒狀態的改變不敏感，且易受抑制性躲避作業的影響。實驗二發現破壞依核殼區同時減抑受試在抬高式十字迷津的危機評估行為、抬高式T形迷津之抑制性躲避行為及制約躲避電擊行為；而破壞依核核區的減抑效果僅見於抬高式T形迷津與制約躲避電擊作業。三個嫌惡作業的結果顯示依核核區與殼區皆涉及制約害怕歷程，但兩區的受損會表現不同焦慮行為，並在抬高式十字迷津之危機評估行為中表現出來。綜合上述二大部分實驗結果，本研究對抬高式T形迷津的行為內涵有更進一步的瞭解，並特別藉依核次級區域破壞的行為測試資料，推估中腦多巴胺系統與傳統理論所指邊緣系統在實證性解釋焦慮具同樣關鍵角色。 / Although anxiety is a well-recognized affective mental reaction, its phenomenon is not fully characterized by the empirical data. By employing a recently developed animal model named the elevated T maze (ETM), the present study investigated the neurobehavioral mechanisms of anxiety. There were two major parts of experiments designed to respectively examine the validity of this task and the involvement of limbic related areas on anxious behavior. Regarding the first part of experiments, Experiment 1A examined the effects of extinction on the inhibitory avoidance of ETM; Experiment 1B evaluated the lesions of six limbic related areas on the measures of inhibitory avoidance and escape; Experiment 1C investigated how pre-exposure experience of stress would affect the ETM behavior; Experiment 1D tested the potential affectiveness derived from different sequences of the test procedure on EMT. The second part of experiments mainly focused on comparing the lesion effects of nucleus accumbens subareas (core and shell) on behavioral measures from three anxiety-related tasks. Elevated plus maze, ETM, and active avoidance were adopted respectively in the experiments of 2A, 2B, and 2C. Results of the first part of experiments indicated 1) inhibitory avoidance of ETM containing fear conditioning and exploration components, and 2) less sensitivity to experimental manipulation for the escape of ETM. In the second part of experiments, the shell lesion significant attenuated the risk assessment behavior of elevated plus maze and inhibitory avoidance of ETM and active avoidance tasks, whereas the core lesion only produced the latter part of impairment. Both core and shell subareas are thus inferred to be involved in the conditioned avoidance, and lesions of these two areas may exert different patterns of anxious behavior. Together, the present study further characterized behavioral components of ETM. With a more systemic work in comparing lesion data of nucleus accumbens over three anxiety-related tasks, it is then suggested that the midbrain dopamine system is as crucial as the traditionally-known limbic system the traditional in terms of providing empirical explanation for the anxiety.

「風險決策」行為非常普遍的存在於吾人之日常生活中，而選項所帶來的風險和獎勵是吾人進行決策時的重要考量因素。風險選擇的適當與否，對於個體的生存扮演著相當重要的角色。在以往的文獻中，對於決策的行為歷程已有所關注及探討，但對於風險選擇行為的神經生理機制迄今未明。本研究藉由大白鼠於T字迷津中，選擇確定之低酬賞或高不確定性之高酬賞的行為表現，進行風險選擇行為的探討。本研究中以兩項主要實驗，探討風險選擇行為之神經行為機制。實驗1a中，確定之低酬賞端固定呈現1顆食物粒，而高不確定性之高酬賞端則同時操弄酬賞物機率(50%、25%及12.5%)以及酬賞物的量(2、4及8顆)，以系統性地檢驗期望值(0.5、1和2)於此風險選擇行為中扮演的角色。行為結果顯示當風險較低時，大白鼠會選擇高不確定性之高酬賞端；而風險較高時，則轉為選擇確定之低酬賞端。實驗1b中，系統性地施打不同劑量之安非他命，探討多巴胺系統在此風險選擇行為中之機制。實驗結果顯示施打安非他命後，大白鼠表現出相對地追求風險之行為，亦即選擇高不確定之高酬賞端之比例顯著高於控制組。實驗2中，藉由毀除大腦特定部位(依核、背外側之紋狀體、眶前額皮質、內側之前額皮質)，檢驗風險選擇行為之神經基礎。毀除後之結果顯示，僅有依核受到毀除之大白鼠表現出相對地趨避風險之選擇行為。綜合以上結果，本研究建立之風險選擇行為與多巴胺有關，而依核在此行為歷程中扮演重要的調節角色。 / Many decisions people make every day involve uncertainty where both risks and rewards associated with each option need to be considered. Behavioral performance associated to risk-based choice appears wildly over the lifespan, and the fitness of risky choice behavior plays an important role in individual survival. Despite a growing body of research has focused to investigate the neurobiology of decision making, little is known about the neurobehavioral mechanisms of risky choice behavior. Based on a pilot work, this study used a T-maze to study decision under a probability-based risk in the rat. The subject was assessed on making choice to obtain either a large reward associated with risk of non-reward “empty” or a small reward ensured for every entry. Two experiments were conducted in this project to investigate neurobehavioral mechanisms of probabilistic risky choice behavior. In Experiment 1a, probabilistic risky choice behavior was systemically assessed under three expected values (0.5, 1.0, and 2.0) by manipulating the probabilities of reward presence (50%, 25%, and 12.5%) and the reward magnitude (2, 4, or 8 pellets) in the probabilistic high reward (PHR) arm. Behavioral data showed that the subject chose the probabilistic high reward in a lower risk condition but would shift to the choice of certain low reward (CLR) as the risk is increased. In Experiment 1b, the dose effects of amphetamine on this probabilistic risky choice task was tested to verify whether the dopaminergic mechanism was involved. Amphetamine, presumably activating brain dopamine systems, produced a relatively risk-seeking effect on the present behavioral task. In Experiment 2, the excitoneurotoxic lesion was conducted in the nucleus accumbens, the dorsolateral striatum, the orbitofrontal cortex, and the medial prefrontal cortex to examine the neural substrates for this probabilistic risky choice behavior. The results showed that the lesion of the nucleus accumbens significantly produced a relatively risk-averse effect on the present behavioral task, as compared to the lesions made on the other three brain areas. In conclusion, the probabilistic risky choice behavior established in the present study is dopamine dependent. And, the nucleus accumbens plays a major role of mediating this behavioral processing.

周邊注射安非它命能夠影響動物受試在表現與時間知覺有關的操作式制約行為作業，歷來被研究者認為是大腦多巴胺神經系統與動物時間知覺系統有關的主要證據之一。本研究所共同採用的研究方法為先注射多巴胺受體專屬拮抗劑再於大鼠受試周邊腹腔注射安非它命的方式探討安非它命影響大鼠時間知覺的大腦機制為何。實驗一利用區辨性增強低頻反應作業觀察周邊注射多巴胺受體專屬拮抗劑何者可以反制周邊安非它命對此作業的影響效果，結果發現多巴胺D1受體拮抗劑SCH23390與D2受體拮抗劑raclopride均可反制周邊安非它命的效果。實驗二同樣利用區辨性增強低頻反應作業，但是將SCH23390與raclopride分別注入海馬迴、背側中區紋狀體、腹側側邊紋狀體、依核、內側前額葉皮質以及腹側頂蓋區等六個部位，觀察何種多巴胺受體拮抗劑可在那些大腦部位產生反制周邊安非它命的效果。結果發現SCH23390可在海馬迴、依核、內側前額葉皮質以及腹側頂蓋區等四個部位產生反制周邊安非它命的效果，而raclopride可在腹側側邊紋狀體與內側前額葉皮質兩個部位產生同樣的反制效果。實驗三利用高峰時距作業觀察SCH23390在海馬迴與內側前額葉皮質是否能反制周邊安非它命對此作業的影響效果，結果發現SCH23390僅在海馬迴會影響大鼠受試的正常表現，特別是在與周邊安非它命同時注射的時候。綜合以上結果顯示，周邊注射安非它命能夠使大鼠受試在區辨性增強低頻反應作業當中表現出時間知覺變快的傾向，這個效果需要同時透過大腦內的海馬迴、依核、內側前額葉皮質以及腹側頂蓋區的多巴胺D1類受體和腹側側邊紋狀體與內側前額葉皮質的多巴胺D2類受體。 / The central dopaminergic system has been hypothesized to play a role in time perception based on the results that peripheral injections of d-amphetamine alter the responses in time-related operant conditioned behavioral tasks. The present study investigated the effect by injecting specific dopamine receptor antagonists before peripheral d-amphetamine injections in rats. Data from Experiment I showed that both peripheral the dopamine receptor D1 antagonist SCH23390 and D2 antagonist raclopride could attenuate the response alteration on differential reinforcement of low-rates responding task induced by peripheral d-amphetamine. By using the DRL task, Experiment 2 employed the microjeciton technique to determine the neural substrates for the DA receptor antagonist to attenuate the effect of peripheral d-amphetamine. The infusion sites for DA receptor antagonist were the hippocampus, the dorsomedial striatum, the ventrolateral striatum, the nucleus accumbens, the medial prefrontal cortex, and the ventral tegme ntal area. The results showed that SCH23390 infused into the hippocampus, the nucleus accumbens, the medial prefrontal cortex, the ventral tegmental area could attenuate the effect induced by peripheral d-amphetamine, and such attenuation effects were also observed for raclopride infused into the ventrolateral striatum, the medial prefrontal cortex. Experiment 3 tried to confirm the results of Experiment 2 by microinjecting SCH23390 in hippocampus and medial prefrontal cortex under peak-interval task. Only SCH23390 in the hippocampus altered the subject's normal performance in this task especially when combined with peripheral injection of d-amphetamine. In conclusion, that the response alteration on the DRL task induced by peripheral injection ofd-amphetamine suggests the subject's timing perception being accelerated. These effects of d-amphetamine were mediated by simultaneous activation of multiple dopamine receptor subtypes including D1 receptors located in the hippocampus, nucleus accumbens, medial pref rontal cortex, ventral tegmental area, as well as D2 receptors located in the ventrolateral striatum, medial prefrontal cortex.