The locus coeruleus (LC) of the rat was lesioned by microinjection of selective neurotoxins into the brainstem. 6‐Hydroxydopamine (6‐OHDA), 3 μg/μl, given unilaterally at two sites 0.6 mm apart on the rostro‐caudal axis of the LC, was used to lesion catecholamine‐containing neuronal elements. Ibotenic acid, 2.5 μg/0.5 μl, administered similarly was used to lesion nerve cell bodies. Two weeks after administration of the neurotoxin, lesion efficacy was determined based on the norepinephrine content of the cerebral cortex ipsi‐ and contralateral to the lesion. 6‐OHDA lesions of the LC caused a 46% reduction in ipsilateral cortical norepinephrine and a 60% reduction in specific 125I‐[Sar1, Ile8]‐angiotensin II (125I‐SIAII) binding in the LC. Ibotenic acid lesions of the LC caused a 73% reduction in ipsilateral cortical norepinephrine and a 81% reduction in specific 125I‐SIAII binding in the LC. These results indicate that All receptor binding sites in the LC are localized on noradrenergic nerve cell bodies or their dendritic and axonal ramifications within the LC.

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.