Abstract

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 characterized the alcohol-specific transcriptional dynamics that regulate these memories. Using a mouse place-conditioning procedure, we found that alcohol memory retrieval increased the expression of Arc and Zif268 in the dorsal hippocampus (DH) and medial prefrontal cortex (mPFC). Alcohol seeking was abolished by post-retrieval non-specific inhibition of gene transcription in the DH, as well as by downregulating ARC expression in the DH using antisense-oligodeoxynucleotides. Since sucrose memory retrieval also increased Arc and Zif268 expression, we performed an RNA-sequencing assay, and revealed alterations in the expression of Adcy8, Neto1, Slc8a3 in the DH and Fkbp5 in the mPFC, caused by the retrieval of alcohol but not sucrose memories. This offers a first insight into the unique transcriptional dynamics underpinning alcohol memory reconsolidation.