Abstract

AimsThe 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 methodsHere 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, 10μM) and morphine (final concentrations 1, 5, 10μM) in human SH-SY5Y cells (at 1h, 24h, 72h, 18days of exposure times). Key findingsThe most important findings are summaries as follow: 1) In the cells treated with morphine, the mRNA level of OPRM1 significantly decreased from 1h to 72h in a dose dependent manner, but it is increased when the cells treated for 18days by high concentrations of morphine; 2) Although the PDYN mRNA level is increased at 1 and 24h (for 5 and 10μM morphine), it is decreased at 72h and 18days; 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. SignificanceDecreasing 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.

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