回首頁 網站導覽
研究新知分享

NMDA 受器促效劑對古柯鹼相關記憶消退的影響

發佈日期：2016/11/24

Authors: 蔡旖旎,Tsai, Yi-Ni
Contributors: 行為醫學研究所
                      游一龍
                      Yu, Lung
日期:2014-08-21
上傳時間:2014-12-30 14:48:22 (UTC+8)

摘要:

古柯鹼相關記憶是造成古柯鹼求藥行為與戒斷藥物後復求行為發生的主要原因。過去研究發現：d-serine這個NMDA receptor的促效劑可以減少古柯鹼相關記憶的表現。而Sodium benzoate 被用於精神分裂症的研究當中，主要是借重其對於d-amino acid oxidase這類d-serine等右旋胺基酸氧化脢的抑制作用，透過抑制d-amino acid oxidase，可以增加突觸間d-serine的含量，加強NMDA receptor的活化。因此，我們決定探討 sodium benzoate 會對古柯鹼相關記憶歷程產生什麼樣的影響。在本研究中，我們探討兩個不同的記憶歷程是否會受到sodium benzoate的影響。(1)古柯鹼相關記憶的再穩固化(reconsolidation)歷程(2)古柯鹼相關記憶的消褪(extinction)歷程。我們使用cocaine-induced conditioned place preference (cocaine-induced CPP)來當作古柯鹼相關記憶的指標。由這些實驗的結果我們可以得到三個結論，第一: sodium benzoate 會干擾古柯鹼相關記憶的再穩固化，進而去減少後續cocaine-induced CPP的表現。第二: sodium benzoate可能是透過作用在medial prefrontal cortex這個腦區去干擾古柯鹼相關記憶的再穩固化。第三: sodium benzoate對於古柯鹼相關記憶的消褪則有加強的效果，sodium benzoate強化了這個新學習記憶的穩固化，進而暫時抑制了cocaine-induced CPP的表現，但是無法降低在reminding test中 cocaine-induced CPP的表現。Sodium benzoate 在 兩種不同記憶歷程中所造成的不同結果，可能需要後續再分析sodium benzoate引發的下游分子訊號的機制才能夠更進一步釐清其中的原因。

Drug-associated memory has been known to reinstate drug-seeking behavior during abstinence and consequently lead to relapse D-serine an endogenous ligand for the glycine site of the NMDA receptor has been documented to interfere cocaine memory expression Sodium benzoate is reported to inhibit the activity of d-amino acid oxidase an enzyme catalyzing d-serine and thus to enhance d-serine accumulation and increase activation of NMDA receptor indirectly In this study we decided to investigate whether sodium benzoate can modulate the drug-associated memory Two paradigms of drug memory processes were used: (1) reconsolidation-related protocol and (2) new learning(extinction)-related protocol Cocaine-induced CPP was used to indicate the cocaine memory Systemic pretreatment with intraperitoneal sodium benzoate at 500 mg/kg (but not 250 mg/kg) before each reconsolidation trail reduced subsequent cocaine-induced CPP magnitude It was of importance to note that such a sodium benzoate treatment did not produce nontargeting effect in subsequent cocaine-induced CPP Moreover such a dosing regimen did not affect locomotor activity in a 30-min free navigation test Furthermore intra-mPFC injections of sodium benzoate before each reconsolidation trail perform a directly effect to reduce cocaine seeking behavior These results taken together suggest that sodium benzoate could be beneficial as a potential medicine of choice in reducing cocaine relapse


來源：成功大學

相關連結1：成功大學

回上一頁