2012年12月6日 讯 /生物谷BIOON/ --近日,来自西安大略大学的研究者揭示了,其通过有效阻断个体记忆或可开发出治疗外伤性神经症(PTSD)以及药物成瘾的新型疗法。这项研究揭示了大脑前边缘皮质区域的一种常见的机制,其可以控制和厌恶相关的大脑回忆。和PTSD相关的创伤性体验以及有益的记忆和药物成瘾直接相关。相关研究成果刊登于国际杂志Neuropharmacology上。
研究者Laviolette表示,这些研究发现对于理解PTSD和药物成瘾非常重要,和这些障碍相关的常见问题就是和害怕相关的回忆再度出现。经历过成瘾的个体经常暴露于环境中,也易于产生药物幻想。研究者表示,他们研究发现了一种大脑的常见机制,其可以控制个体对于厌恶记忆以及药物成瘾经历的回忆。
在实验中,研究者使用小鼠模型进行研究发现,在大脑特殊区域刺激多巴胺受体D1受体的亚型可以完全抑制个体对于厌恶相关回忆的产生,大脑中这种精确的机制可以控制这些记忆是否会被个人记忆起来,当前并没有有效的疗法来治疗和PTSD相关的强迫性记忆症。如果我们可以阻断这些不好回忆的产生,那么我们就可以开发出靶向疗法来针对这些障碍了。
在电影《美丽心灵的永恒阳光》中,演员们试图永远擦去大脑中的感情记忆,研究者Laviolette表示,我们的研究发现就可以通过抑制大脑记忆的自发性回忆,但是这种记忆在大脑中确实完整无损的。(生物谷Bioon.com)
doi:10.1016/j.neuropharm.2012.10.029
PMC:
PMID:
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.