本研究利用兩種時間關聯之操作式制約行為作業探討韁核的行為功能，一為區辨性增強低頻反應作業（簡稱DRL作業），另一為固定時距作業（簡稱FI作業）。本研究以神經毒素鵝膏蕈酸（ibotenic acid）破壞韁核的方式來測試大白鼠受試在上述行為作業之不同歷程的影響效果，包含習得歷程、行為表現階段以及已習得後轉換得酬賞之反應標準等三個階段。實驗一的結果顯示破壞韁核對於DRL作業的習得歷程具有明顯的影響，其影響效果在DRL短時距作業中造成無法以有效率的壓桿反應模式獲得酬賞；反之，破壞操弄的效果並不影響FI長與短時距作業的習得歷程。實驗二的結果顯示破壞韁核並不影響已習得的DRL作業與FI作業的行為表現，兩項作業的實驗組受試皆能維持穩定的行為反應模式且與控制組無明顯差異。實驗三對已習得的DRL行為進行時距參數的轉換（含調高及降低兩部份），結果顯示破壞韁核之操弄並未明顯的影響這項轉換新的時距之作業要求，但實驗組受試的確比控制組較遲緩達到新的時距要求。綜合而言，本研究以專屬性較高的神經毒素破壞韁核，用較多元指標的行為分析方式探討韁核的行為功能；其結果發現韁核參與DRL行為內含的區辨學習與對於錯誤偵測的負向迴饋，這些功能是需要透過韁核與其他中腦及邊緣系統的組織互動。 / This study examined the function of habenula (Hb) by two kinds of operant conditioned behavior tasks based on temporal contingency, including the differential reinforcement of low-rate responding (DRL) task and fixed-interval (FI) task. The effects of Hb lesion induced by neurotoxin ibotenic acid were examined at the different stages of operant conditioned behavior, including acquisition, performance, and transition stages. The results showed that bilateral lesions of Hb did not affect the locomotor activity and the basic lever-pressing. In Experiment 1, Hb lesion group had less reinforced responses and lower peak time indicating the deficits of acquisition of the DRL task. In contrast, the same lesion manipulation on the FI task did not produce any difference between the lesion group and the control group. The data of Experiment 2 showed that Hb lesion did not significantly affect the learned behavior maintained on DRL-10s or FI-30s schedule. In Experiment 3, Hb lesion produced a subtle, but not significant, impairment on behavioral transition from a learned interval to a newly-set interval (upward or downward). The lesioned subjects made a slower transition than the controls. In conclusion, these data suggest that the function of habenula is involved in discrimination learning and error detection for acquiring DRL behavior. However, it is likely that these Hb functions have to rely upon dynamic relationship between Hb and other midbrain limbic systems.

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.