以微量注射探討大鼠大腦皮質觸覺神經元的愷他命劑量反應曲線

Abstract

觸覺及傷害覺是人類和動物生存上必不可少的感受。但由於中樞神經系統是由成千上萬神經元組成並相互運作及影響，至今尚未完全瞭解大腦如何處理這兩種信號。本實驗室因此長年致力於體感覺神經元的研究。 愷他命是年輕族群藥物濫用比例最高的毒品。並且具有意識分離麻醉劑、誘導思覺失調症的動物模型藥物，甚至抗憂鬱症短期治療藥物等功能。然而，過去對於愷他命的研究多通過靜脈注射愷他命，此種方式無法確定是否完全是量測區域神經元對藥物的反應，亦或是神經傳導路徑上區域的相互影響。本實驗室於2017年研究使用的多孔道玻璃微電極，於目標神經元旁微量注射藥物，不僅解決上述問題，甚至進一步研究愷他命對於視丘觸覺神經元的影響。 本研究將探討愷他命對於大腦皮質觸覺神經元的影響，除了與視丘神經元研究的結果做比較外，也將探討不同愷他命劑量對於神經元活性變化的差異，並觀察多次於恢復後注射愷他命是否對神經元活性變化程度產生影響。此外，為了能確保記錄反應曲線的準確性，將運用相關係數分析找尋適當的採樣間隔時間。 實驗結果顯示，首先，對照組注射生理食鹽水，證明神經元活性變化與注射操作在時間上無相關性。其次，神經元活性變化主要受到劑量的影響，而非體積與濃度。三種愷他命劑量都使神經元活性降至40 % 以下，對於大腦皮質神經元抑制程度相近，並且多次於恢復後注射愷他命的抑制程度亦同。最後，與視丘神經元的研究相比較，在相同的愷他命劑量下，皮質神經元被抑制程度明顯更加強烈。

Human and animals cannot survive without tactile sense and the systems of nociception, However, animals’ central nervous system is composed of thousands of collaborative neurons, and how the brain processes these two signals is not yet fully understood. Then our laboratory has been devoted to the research of somatosensory neurons for many years. Ketamine is the most frequently misused drug among the adolescent group. Ketamine also functions as dissociative anesthetics, the medicine for the animal model of schizophrenia, and the antidepressant as a short-term drug treatment. However, most of the previous studies about ketamine focused on the effects of an intravenous injection of ketamine, but these studies could not determine whether the neuropathway was fully inflicted by ketamine, or simply being inflicted by the areas along the neuropathway. The two-barrel microelectrodes, developed by our laboratory, can microinject into the target area, and this method not only solves the above concerns, but also explores the effects of ketamine on the thalamus tactile neurons. In addition to comparing with the previous studies, the aim of this study was to explore the effects of ketamine on the cortical tactile neurons and to analyze how different dose of ketamine could cause the variations of neuronal activities even after repeated injections of ketamine after 30 minutes’ recovery time. Moreover, in order to ensure the accuracy of the response curve, this study used the correlation coefficient to find an appropriate sampling interval time. This experiment showed, first of all, the control group was injected with saline, which proved that there was no correlation between the variations of neuronal activities and the injection operation in terms of time. Second, the variations of neuronal activities were mainly affected by dose, rather than volume and concentration. The three doses of ketamine all reduced the neuron activity to below 40%, and the inhibition of cortex neurons was similar, and the extent of inhibition of ketamine injection after recovery was also the same. Finally, compared with the study of thalamic neurons, cortical neurons were inhibited significantly using the same dose of ketamine.