多巴胺的神經行為功能-探討內側前額葉皮質處多巴胺在壓力下的角色

• Main Author: 沈映伶
• Language: 中文
• Published: 國立政治大學
• Subjects: 禁錮壓力源; 場地制約偏好行為; 倒序制約; 同時制約; SCH23390; raclopride
• Online Access: http://thesis.lib.nccu.edu.tw/cgi-bin/cdrfb3/gsweb.cgi?o=dstdcdr&i=sid=%22G0917525021%22.

本研究為能瞭解多巴胺在壓力源引發個體古典制約行為學習中的參與角色，採用一個與多巴胺相關的場地制約偏好行為作為研究工具，並利用一較溫和的禁錮壓力源作為非制約刺激與場地環境制約刺激進行配對制約。本研究假設內側前額葉皮質處的多巴胺參與在此壓力源引發場地制約行為學習中。實驗一針對單次禁錮壓力源的非制約刺激效果進行檢驗，分別檢測壓力源對個體的生理、情緒或是行為活動量的影響。實驗二利用「同時制約」或是「倒序制約」等兩種制約方式來進行單次禁錮壓力源引發場地制約偏好行為作業，並分別於制約程序的不同時間點施予多巴胺專屬受器拮抗劑，檢驗多巴胺在制約行為學習作業中的參與。實驗三在「同時制約」或是「倒序制約」兩種制約程序中的不同時間點，施予局部麻醉藥物二丁卡因暫時抑制內側前額葉皮質活動，以檢驗該區塊在單次禁錮壓力源引發場地制約偏好行為下的參與角色。實驗四為了解內側前額葉皮質處多巴胺在單次禁錮壓力源引發場地制約偏好行為中的角色，在「同時制約」程序的不同時間點施打多巴胺專屬受器拮抗劑至內側前額葉皮質區。 實驗結果發現：本研究所使用的單次30分鐘禁錮壓力源，確實可以引發實驗動物體內的壓力賀爾蒙糖皮質素大量增加、提高焦慮情緒或是降低自發性行為活動量。單次禁錮壓力源在「同時制約」或是「倒序制約」等兩種制約程序下，都能建立場地制約偏好行為。在禁錮壓力源操弄「之前」或「之後」，周邊施打多巴胺D1或是D2專屬受器拮抗劑，在「同時制約」或是「倒序制約」兩種制約程序中都會減抑禁錮壓力源建立場地制約偏好行為的效果。在「倒序制約」方式中，在「實驗動物接受完30分鐘壓力源操弄後被置入制約箱之前」才給予多巴胺拮抗劑，也會破壞後續的配對制約形成。在中樞內側前額葉皮質部分，在「同時制約」或是「倒序制約」兩種制約程序中，二丁卡因在壓力源與環境刺激配對「之前」給予才會抑制禁錮壓力源建立場地制約偏好行為的效果。在壓力源與環境刺激配對「之後」才抑制該處神經活動則不影響壓力源建立制約行為的效果。中樞內側前額葉皮質施予多巴胺D1或是D2專屬受器拮抗劑，也得到前述相同實驗結果。 本研究的實驗結果證明單次禁錮壓力源確實可以建立場地制約，為另類的古典制約行為。壓力源的操弄可引發多巴胺釋放量增加，及內側前額葉皮質處的多巴胺確實參與了此禁錮壓力源引發場地制約偏好行為。總結本研究結果顯示內側前額葉皮質處多巴胺在壓力下會對制約行為學習造成影響，並冀望此結果可以擴展對於內側前額葉皮質功能失能與心智疾患間關係的瞭解。在演化上，壓力對於人類或是其他族群的生存有其必要性。動物對於其環境中的危險或是威脅事件必須進行行為學習或因應，才能避免生命的損失。 === To investigate the role of dopamine in stressor involved in classical conditioning, the present study used a dopamine-related task, conditioned place preference (CPP), as behavioral measurement. The mild restraint stressor was used and presumed to serve as the unconditioned stimulus to be paired with the contextual conditioned stimulus. The medial prefrontal cortex (mPFC) was hypothesized to be involved in this type of stressor induced place conditioning. Experiment 1 examined the effects of restraint stressor on physiological, emotional or locomotor tests. Experiment 2 investigated the involvement of dopamine in the stressor induced CPP, which conditioning procedures were manipulated by either simultaneous or backward form. The selective dopamine receptor antagonists were systemically administered in different time points during the conditioning procedures. Experiment 3 took lidocaine, a local anesthetic, to induce temporal deactivation of the mPFC. Lidocaine was infused in the mPFC at various time points, in either simultaneous or backward conditioning, to evaluate the involvement of the mPFC in stressor induced place conditioning. To further investigate the effects of dopamine receptors in the mPFC in the present type of CPP, the selective dopamine receptor antagonists were locally infused into the mPFC in simulutaneous conditioning procedure in Experiment 4. The results showed that the manipulation of acute 30 min. restraint stressor increased the corticosterone, anxiety, but reduced the locomotor activities in rats. Consitent with previous work, this acute restraint stressor treatment given in either simultaneous or backward conditioning form significantly induced CPP. Systemic injection of dopamine D1 or D2 receptor antagonist given “before” or “after” the manipulation of restraint stressor, in either simultaneous or backward conditioning, attenuated the formation of stressor induced CPP. When these drugs were infused “right after the stressor manipulation and before the commencement of place conditioning” in the backward conditioning, the induction of CPP was also impaired. The attenuation of stressor formed place conditioning was showed when lidocaine was infused in the mPFC “before”, but not “after” the manipulation of restraint stressor. Such an attenuation effect was also seen when the selective D1 or D2 dopamine antagonist was infused in the mPFC. The present study showed restraint stressor induced place conditioning as a novel type of classical conditioning. Consistent with the evidence showing that the manipulation of this stressor increases the release of dopamine, this study further verifed that the dopamine in the mPFC is involved in this restraint stressor induced CPP.