School of Psychological Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.
Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, 10027, USA.
Transl Psychiatry. 2023 Feb 15;13(1):55. doi: 10.1038/s41398-023-02352-2.
Relapse, a critical issue in alcohol addiction, can be attenuated by disruption of alcohol-associated memories. Memories are thought to temporarily destabilize upon retrieval during the reconsolidation process. Here, we provide evidence for unique transcriptional dynamics underpinning alcohol memory reconsolidation. Using a mouse place-conditioning procedure, we show that alcohol-memory retrieval increases the mRNA expression of immediate-early genes in the dorsal hippocampus and medial prefrontal cortex, and that alcohol seeking is abolished by post-retrieval non-specific inhibition of gene transcription, or by downregulating ARC expression using antisense-oligodeoxynucleotides. However, since retrieval of memories for a natural reward (sucrose) also increased the same immediate-early gene expression, we explored for alcohol-specific transcriptional changes using RNA-sequencing. We revealed a unique transcriptional fingerprint activated by alcohol memories, as the expression of this set of plasticity-related genes was not altered by sucrose-memory retrieval. Our results suggest that alcohol memories may activate two parallel transcription programs: one is involved in memory reconsolidation in general, and another is specifically activated during alcohol-memory processing.
复发是酒精成瘾的一个关键问题，可以通过破坏与酒精相关的记忆来减轻。人们认为记忆在再巩固过程中被检索时会暂时变得不稳定。在这里，我们提供了支持酒精记忆再巩固的独特转录动力学的证据。使用小鼠位置条件反射程序，我们表明，酒精记忆检索会增加背侧海马体和内侧前额叶皮质中即刻早期基因的 mRNA 表达，并且通过在检索后非特异性抑制基因转录，或者使用反义寡核苷酸下调 ARC 表达，可消除酒精寻求。然而，由于对自然奖励（蔗糖）的记忆检索也增加了相同的即刻早期基因表达，我们使用 RNA 测序探索了酒精特异性转录变化。我们揭示了一组由酒精记忆激活的独特转录指纹，因为这组与可塑性相关的基因的表达并未因蔗糖记忆检索而改变。我们的研究结果表明，酒精记忆可能会激活两个平行的转录程序：一个程序涉及一般的记忆再巩固，另一个程序则在酒精记忆处理过程中特异性激活。
