Expression levels of OPRM1 and PDYN in human SH-SY5Y cells treated with morphine and methadone

Aims: The opioid receptor mu-1 (OPRM1, site of action for methadone and morphine, OMIM: 600018) and prodynorphin (PDYN, OMIM: 131340) genes are belonging to the endogenous opioid family. There is no data on alterations of mRNA levels of PDYN and OPRM1 in cells exposed to methadone. Therefore, the present study was carried out. Main methods: Here we have investigated the alterations of the expression levels of OPRM1 and PDYN genes in response to methadone (final concentrations 1, 2.5, 5, 7.5, 10 mu M) and morphine (final concentrations 1, 5, 10 mu M) in human SH-SY5Y cells (at 1 h, 24 h, 72 h, 18 days of exposure times). Key findings: The most important findings are summaries as follow: 1) In the cells treated with morphine, the mRNA level of OPRM1 significantly decreased from 1 h to 72 h in a dose dependent manner, but it is increased when the cells treated for 18 days by high concentrations of morphine; 2) Although the PDYN mRNA level is increased at 1 and 24 h (for 5 and 10 mu M morphine), it is decreased at 72 h and 18 days; 3) The mRNA level of OPRM1 negatively is associated with a methadone dose dependent and exposure time dependent manner; 4) In overall, the PDYN mRNA level is increased in the treated cells without any obvious trend by dose of methadone or exposure time. Significance: Decreasing the PDYN mRNA levels in cells exposed to morphine for long period times, and increasing the level of PDYN mRNA in methadone treated cells, can interpret why heroine-dependent persons, easily accept methadone therapy. (C) 2016 Elsevier Inc. All rights reserved.