IncRNA expression profiles in the striatum of morphine tolerant rats

Background and Aim: Morphine tolerance is a challenging clinical problem that limits the use of morphine in pain treatment. However, mechanisms of morphine tolerance remain unclear. According to recent researches, long noncoding RNAs (lncRNAs) might be a novel and promising target in the pathogeneses of morphine tolerance and addiction, as well as new clinical biomarkers for the diseases. Striatum including nucleus accumbens is a main target of the mesocorticolimbic pathway, which is involved in morphine tolerance and addiction. However, there is no report about IncRNAs expressions in the striatum of morphine-tolerant subjects. Methods: We used male Wistar rats in our study. Morphine (۱۰ mg/kg) was injected twice daily for ۸ days for inducing morphine tolerance. A control group received saline (۱ ml/kg) during the treatments. We tested animals for induction of morphine tolerance on a hotplate test of analgesia on day ۸ of the treatments. On day ۸, each rat was anesthetized, decapitated and the striatum was dissected on an ice-chilled surface. The expression of lncRNAs, including MALATI, BC۱, NEAT۱, MIAT۱, Hypothalamus-enriched IncRNA and Cardiac left ventricle-enriched IncRNA was assessed by using a real-time qPCR method. We analyzed the hotplate data with a two-way repeated measure ANOVA followed by Holm-Sidak post hoc test. We also converted the Ct values of real time q-PCR data to ۲-AACT, and then used an independent t-test for pairwise between groups comparisons. P<۰.۰۵ was considered as statistically significant level. Results: In this study, we examine expression of some IncRNAs in the striatum of morphine-tolerant rats. Conclusion: The rats successfully developed morphine tolerance as revealed by the results of the hotplate test of analgesia (P<۰.۰۰۱). The results of the real-time PCR indicated that the expressions of MALATI, NEAT۱ and BC۱ IncRNAs were not affected in the striatum of morphine-tolerant rats compared to the control group. However, the qPCR results revealed that the expression of MIATI and Cardiac left ventricle-enriched IncRNA was significantly increased (P<۰.۰۵) but the expression of Hypothalamus-enriched IncRNA was significantly decreased (P<۰.۰۱) in the striatum of morphine-tolerant rats compared to the control group.

کلیدواژه ها:

Morphine tolerance ، Analgesia ، IncRNAs ، Gene regulation ، rat