Two kinds of transcription factors mediate chronic morphine-induced decrease in miR-105 in medial prefrontal cortex of rats

Chronic morphine administration alters gene expression in different brain regions, an effect which may contribute to plastic changes associated with addictive behavior. This change in gene expression is most possibly mediated by addictive drug-induced epigenetic remodeling of gene expression programs. Our previous studies showed that chronic morphine-induced decrease of miR-105 in the medial prefrontal cortex (mPFC) contributed to context-induced retrieval of morphine withdrawal memory. However, how chronic morphine treatment decreases miR-105 in the mPFC still remains unknown. The present study shows that chronic morphine induces addiction-related change in miR-105 in the mPFC via two kinds of transcription factors: the first transcription factor is CREB activated by mu receptors-ERK-p90RSK signaling pathway and the second transcription factor is glucocorticoid receptor (GR), which as a negative transcription factor, mediates chronic morphine-induced decrease in miR-105 in the mPFC of rats.

Automated summary

Chronic morphine administration causes changes in gene expression in different brain regions, potentially contributing to the plasticity associated with addictive behavior. This change in gene expression is most likely mediated by addictive drug-induced epigenetic remodeling of gene expression programs. Previous studies have shown that chronic morphine treatment decreases the levels of miR-105 in the medial prefrontal cortex (mPFC), which is involved in context-induced retrieval of morphine withdrawal memory. However, the mechanism through which chronic morphine treatment decreases miR-105 in the mPFC remains unknown. The present study reveals that chronic morphine induces addiction-related changes in miR-105 in the mPFC through the activation of two transcription factors: CREB, activated by mu receptors-ERK-p90RSK signaling pathway, and glucocorticoid receptor (GR), which acts as a negative transcription factor mediating the decrease in miR-105 levels in the mPFC of rats.