新生期投予Dexamethasone 對大白鼠成年期杏仁核功能之影響

No Thumbnail Available

Date

2009

Journal Title

Journal ISSN

Volume Title

Publisher

Abstract

人類於新生期所面對的心理或生理壓力,會對成年期的情緒表達或生理狀況產生深遠的影響。Dexamethasone(DEX)為一種人工合成的醣皮質激素,常用於早產兒的治療,它可有效的降低早產兒因肺部發育不良所引發的慢性呼吸系統疾病 (chronic lung disease)。近期研究顯示在大白鼠新生期投予 DEX 可能導致青少年期空間記憶產生障礙,亦會干擾海馬迴 (hippocampus) 中長期增益現象 (long-term potentiation;LTP) 的形成。而這些不良影響在成年期可獲得改善。新近的研究結果指出,新生期投予 DEX 亦可能使下視丘-腦下垂體-腎上腺機制(hypothalamo–pituitary–adrenal;HPA axis) 失調導致情緒或恐懼記憶造成影響。因此,本研究利用 Wistar 大白鼠,於出生後第一至第三天,以皮下注射的方式遞減式的投予 DEX。結果顯示新生期投予 DEX,體重增幅明顯趨緩,但在六週後此現象逐漸消失。新生期投予 DEX 之大白鼠在八週仍會抑制杏仁核長期增益現象。自發性運動行為及平衡桿測試的表現並沒有顯著差異,故藥物之投予並不影響動物的活動力或基本的運動功能。強迫游泳測試 (forced swimming test;FST) 發現,新生期投予 DEX 的大白鼠在短時間內即放棄掙扎,在水中靜止與漂浮的時間較長,且經曝露高台 (exposed of flat-top) 的刺激後,實驗組大白鼠漂浮時間顯著增長,並達顯著差異。因此在壓力刺激下,可能會增加其憂鬱行為表現。動物由恐懼所促進之驚跳反應 (fear potentiated startle;FPS) 的行為模式結果顯示,動物在新生期接受 DEX確實影響大白鼠成年後條件化恐懼記憶 (fear condition) 的建立,使之無法形成。由結果可推論,新生期接受 DEX 注射會影響成鼠杏仁核形成長期增益現象。新生期 DEX 投予雖不影響動物活動力與運動功能,但曝露於壓力情境下,會較易顯現出憂鬱之傾向,並且干擾動物對外界線索的連結,影響條件化恐懼記憶的形成。綜合此等結果,我們認為新生期投予 DEX 對於動物杏仁核神經傳導活性之神經可塑性、壓力引起的情緒反應以及條件化恐懼記憶的形成皆會造成顯著影響,且可延續至成年期。
Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Previous studies suggest neonatal DEX treatment altered hippocampal synaptic plasticity and associative memory in rats. It has been recognized that the amygdala is highly involved in emotional processes. In fact, considerable evidence suggests that the amygdala may be a critical site of neuronal plasticity for fear learning. The present study was aimed to evaluate the possible effects of neonatal DEX treatment on the synaptic function of amygdala in adult rats. To achieve this goal, we were subcutaneous injection (sc) of tapering doses of DEX from postnatal day 1 to 3, PN1~PN3. Animals were then subjected for electrophysiological recording, forced swimming test (FST) and fear potentiated startle (FPS) at the age of 8 weeks. Results showed that neonatal DEX treatment temporary decrease body weight in the young rats, but not affected in the later life when compared with the control group. Neonatal DEX treatment blocked LTP formation in basolateral nucleus of amygdala. Locomotor activity and rota-rod results showed that neonatal DEX treatment did not affect animal’s motor function. Neonatal DEX treatment also increased depression-like behavior in adulthood which had been determined by using FST. The percentage of time spent in free floating is significant increased via exposed of flat-top in the DEX treated group compared with the control animals. Furthermore, fear potentiated startle evidence that neonatal DEX treatment to hold back formation of fear condition in adulthood. Our results suggest that neonatal DEX treatment may have adverse consequence in the later life. The resulted gathered from this study not only expand our knowledge on the neural basis of fear learning, but also help us to know how neonatal stress may alter the neuroplasticity in amygdala . The conclusion that enhancement of the susceptibility for depression disorder and wrong to connect with fear condition in later life.

Description

Keywords

Dexamethasone (DEX), 長期增益現象, 高台曝露, 強迫游泳, 恐懼驚嚇反應, 杏仁核, Dexamethasone(DEX), long-term potentiation (LTP), exposed of flat-top, forced swimming test (FST), fear potentiated startle (FPS), amygdala

Citation

Collections

Endorsement

Review

Supplemented By

Referenced By