以跨領域取向探討青少年期經歷長期社交挫敗對成年之影響-以雄性敘利亞倉鼠為模式

Abstract

長期經歷社會壓力增加日後心理疾患發展的風險。社交挫敗在青少年階段是一個強力的壓力源並造成行為與神經內分泌的改變。動物模式提供研究者一個可操作且直觀的方式用以了解個體在經歷社會壓力後的行為與生理反應變化。為了解青少年期長期社交挫敗在行為、生理、內分泌、免疫與神經化學之影響，本實驗利用雄性敘利亞倉鼠之自發性攻擊行為設計五個實驗。雄性青少年期倉鼠(出生後28天)被隨機分配到以下三組:社交挫敗組、社交威脅組與情境控制組，並在出生後33天到66天根據其組別接受9次相對應的社交互動試驗。在實驗一中，透過在三種不同試驗情境下的行為表現，分別於第一次社會互動後接受短期效果測驗，並於最後一次社會互動後接受長期效果測驗。實驗結果發現:長期社交屈從經驗(而非在第一次社交屈從)會對雄鼠行為造成改變。實驗二與實驗三分別記錄在經歷短期與長期社交挫敗後的生理指標與內分泌指標。實驗二發現:青少年期社交挫敗經驗不影響雄鼠的基礎生理指標，但長期社交挫敗經驗在雄鼠上會造成脾腫大的現象。實驗三發現:長期社交挫敗經驗會顯著增加雄鼠血液中的可體松(cortisol)與正腎上腺素濃度。實驗四利用免疫微珠陣列法(cytometric beads array method)分析不同腦區內的發炎前驅細胞激素表現以評估免疫反應。實驗結果發現: 經歷長期社交挫敗影響不同腦區中的介白素1β (IL-1β)、介白素6 (IL-6)與腫瘤壞死因子α (TNF-α)之調節。實驗五檢驗不同腦區的單胺類神經傳導物質。實驗結果發現雄鼠的長期社交挫敗經驗會有腦區專一性的影響，特別是多巴胺與血清素在紋狀體與海馬迴的表現。綜合以上所述，本倉鼠模式在研究社交挫敗議題上提供些許優勢，並發現青少年期經歷長期社交挫敗在不同層次上之影響可延續至成年。

Chronic social stress is involved in the increasing risk for the development of psychopathology. Social defeat is a potent stressor that produces numerous behavioral and neuroendocinal alternations, especially during juvenile period. Animal models provide a relatively manageable and straightforward approach to study behavioral and physiological consequences after experiencing social defeats. To understand the impact of chronic social defeat during juvenile stage on behavioral, physiological, hormonal, immune and neurochemical responses, we take advantage of male Syrian hamsters and their agonistic behavior to design a serial of 5 experiments in this study. Juvenile (postnatal day 28) male hamsters were randomly assigned into one of the following three groups: the social defeat group, the social threaten group, or the arena control group. Males in different groups received a series of 9 social interaction trials during juvenile period from postnatal days 33-66. In Experiment 1, their behavioral performances were evaluated in 3 different testing contexts for acute and chronic tests after experiencing the 1st and the last social interaction trials, respectively. The experience of a series of social defeat (rather than the 1st social defeat) had significant impact on the behavioral responses in male hamsters. Experiment 2 and 3 were conducted to assess physiological and hormonal indexes after experiencing acute and chronic social defeat. In Experiment 2, neither a series of social defeat nor the 1st defeated experience affected basic physiological responses but the chronic defeated experience had significant impact on the enlargement of spleen. In Experiment 3, the experience of chronic social defeat significantly enhanced cortisol and norepinephrine concentrations in the blood of hamsters. In Experiment 4, pro-inflammatory cytokine levels in different brain areas were measured to reveal immune responses using cytometric beads array. Our data revealed that such chronic defeat experience had differential effects on the regulation of IL-1β, IL-6, and TNF-α expressions in different brain areas. In Experiment 5, monoamine neurotransmitter levels in different brain areas were examined. We found that chronic defeat experience had a region-specific impact on the alterations of dopamine and 5-HT levels in the brains of male hamsters, especially in the striatum and hippocampus. Collectively, our hamster model offers several advantages for studying social defeat and our data indicate that the experience of chronic social defeat during juvenile period has multiple levels of impact on adult male hamsters.