2012年12月6日 訊 /生物谷BIOON/ --近日,，來自西安大略大學(xué)的研究者揭示了,，其通過有效阻斷個體記憶或可開發(fā)出治療外傷性神經(jīng)癥（PTSD）以及藥物成癮的新型療法。這項研究揭示了大腦前邊緣皮質(zhì)區(qū)域的一種常見的機(jī)制,，其可以控制和厭惡相關(guān)的大腦回憶,。和PTSD相關(guān)的創(chuàng)傷性體驗以及有益的記憶和藥物成癮直接相關(guān)。相關(guān)研究成果刊登于國際雜志Neuropharmacology上,。
研究者Laviolette表示,，這些研究發(fā)現(xiàn)對于理解PTSD和藥物成癮非常重要，和這些障礙相關(guān)的常見問題就是和害怕相關(guān)的回憶再度出現(xiàn),。經(jīng)歷過成癮的個體經(jīng)常暴露于環(huán)境中,，也易于產(chǎn)生藥物幻想。研究者表示,，他們研究發(fā)現(xiàn)了一種大腦的常見機(jī)制,，其可以控制個體對于厭惡記憶以及藥物成癮經(jīng)歷的回憶。
在實驗中,，研究者使用小鼠模型進(jìn)行研究發(fā)現(xiàn),，在大腦特殊區(qū)域刺激多巴胺受體D1受體的亞型可以完全抑制個體對于厭惡相關(guān)回憶的產(chǎn)生，大腦中這種精確的機(jī)制可以控制這些記憶是否會被個人記憶起來,，當(dāng)前并沒有有效的療法來治療和PTSD相關(guān)的強(qiáng)迫性記憶癥,。如果我們可以阻斷這些不好回憶的產(chǎn)生，那么我們就可以開發(fā)出靶向療法來針對這些障礙了,。
在電影《美麗心靈的永恒陽光》中,，演員們試圖永遠(yuǎn)擦去大腦中的感情記憶,，研究者Laviolette表示，我們的研究發(fā)現(xiàn)就可以通過抑制大腦記憶的自發(fā)性回憶,，但是這種記憶在大腦中確實完整無損的,。（生物谷Bioon.com）
doi:10.1016/j.neuropharm.2012.10.029
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Supra-normal stimulation of dopamine D1 receptors in the prelimbic cortex blocks behavioral expression of both aversive and rewarding associative memories through a cyclic-AMP-dependent signaling pathway
Nicole M. Lauzona, b, Melanie Becharda, b, Tasha Ahmada, b, Steven R. Laviolettea, b, ,
Dopamine (DA) receptor transmission through either D1 or D2-like subtypes is involved critically in the processing of emotional information within the medial prefrontal cortex (mPFC). However the functional role of specific DA D1-like receptor transmission in the expression of emotionally salient associative memories (either aversive or rewarding) is not currently understood. Here we demonstrate that specific activation of DA D1 receptors in the prelimbic (PLC) division of the mPFC causes a transient block in the behavioral expression of both aversive and rewarding associative memories. We report that intra-PLC microinfusions of a selective D1 receptor agonist block the spontaneous expression of an associative olfactory fear memory, without altering the stability of the original memory trace. Furthermore, using an unbiased place conditioning procedure (CPP), intra-PLC D1 receptor activation blocks the spontaneous expression of an associative morphine (5 mg/kg; i.p.) reward memory, while leaving morphine-primed memory expression intact. Interestingly, both intra-PLC D1-receptor mediated block of either fear-related or reward-related associative memories were dependent upon downstream cyclic-AMP (cAMP) signaling as both effects were rescued by co-administration of a cAMP signaling inhibitor. The blockade of both rewarding and aversive associative memories is mediated through a D1-specific signaling pathway, as neither forms of spontaneous memory expression were blocked by intra-PLC microinfusions of a D2-like receptor agonist. Our results demonstrate that the spontaneous expression of either rewarding or aversive emotionally salient memories shares a common, D1-receptor mediated substrate within the mPFC.
