| Summary: | Impairing reconsolidation may disrupt drug memories to prevent relapse, meanwhile long-term transcription regulations in the brain regions contribute to the occurrence of emotional memories. The basolateral amygdala (BLA) is involved in the drug-cue association, while the nucleus accumbens (NAc) responds to the drug reward. Here, we assessed whether DNA methyltransferases (Dnmts) in these two brain regions function identically in the reconsolidation of morphine reward memory. We show that Dnmts inhibition in the BLA but not in the NAc after memory retrieval impaired reconsolidation of a morphine reward memory. Moreover, the mRNA levels of <i>Dnmt3a</i> and <i>Dnmt3b</i>, rather than <i>Dnmt1</i>, in the BLA were continuously upregulated after retrieval. We further identified the differentially methylated regions (DMRs) in genes in the BLA after retrieval, and focused on the DMRs located in gene promoter regions. Among them were three genes (<i>Gnas</i>, <i>Sox10</i>, and <i>Pik3r1</i>) involved in memory modulation. Furthermore, <i>Gnas</i> promoter hypermethylation was confirmed to be inversely correlated with the downregulation of <i>Gnas</i> mRNA levels. The findings indicate that the specific transcription regulation mechanism in the BLA and NAc on reconsolidation of opiate-associated memories can be dissociable, and DNA hypermethylation of <i>Gnas</i> in the BLA is necessary for the reconsolidation of morphine reward memories.
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