mir-33-5p regulates creb to induce morphine state-dependent memory in rats: interaction with µ opioid receptor

The aim of the present study was to examine the hypothesis that mir-33-5p attenuates morphine state-dependent (std) memory via the µ opioid receptor by regulating cyclic amp response element-binding protein (creb). the effects of post-training morphine and morphine std memory and their interaction with pre-test naloxone were evaluated using a single-trial inhibitory avoidance paradigm. then, the hippocampal mir-33-5p gene and pcreb/creb protein expression profiles were evaluated using quantitative real-time pcr and western blotting, respectively. we found that while post-training morphine and morphine std memory respectively up- and down-regulate the mir-33-5p expression profile in the hippocampus, the reverse results are true for the expression of pcreb/creb. pre-test naloxone antagonized the response. overall, our findings suggest that the expression levels of mir-33-5p in the hippocampus set the basis for morphine std memory with low mir-33-5p enabling state dependency. the mechanism is mediated via mir33-5p and creb signaling with the interaction of the µ opioid receptor. this finding may be used as a potential strategy for ameliorating morphine-induced memory-related disorders.