Regulation of MOR‐1 variants during chronic morphine exposure in differentiated and undifferentiated SH‐SY5Y neuroblastoma cells (803.9)

Abstract

Morphine and other analgesic drugs play a crucial role in pain modulation therapy. Morphine is an effective analgesic that functions by binding to the mu‐opioid receptor (MOR). Chronic administration of morphine leads severe side effects such as respiratory depression and the development of tolerance. There are several hypotheses about the development of tolerance, which include internalization, down regulation, and phosphorylation. Studies have identified several MOR‐1 variants, however their function is still unclear. The present study explores the regulation of the MOR‐1 spliced variant forms Mor1A, MorB1, B2, B3, B5 and Mor1‐K1 after chronic treatment with morphine (in differentiated and undifferentiated SH‐SY5Y neuroblastoma cells. The SH‐SY5Y cells were grown in (1:1) DMEM/F‐12 media at 37°C, 95%air/5%CO2 and differentiated to a mature neuronal cell type using Retinoic acid (10μM) for six days. The cells where chronically treated with morphine (10μM) for 24 hours. Real‐time quantitative RT‐PCR is used to determine the changes in MOR‐1 and its variants expression. The results revealed that chronic morphine treatment caused a significant decrease in the MOR‐1 gene expression of differentiated SH‐SY5Y cells. Further studies will be performed to see if the expression of the MOR‐1 variants is also regulated after chronic morphine treatment in the SH‐SY5Y cells. In conclusion, these findings show that human SH‐SY5Y neuroblastoma cells serve as a useful model to investigate MOR‐1 variants and their role in opioid tolerance.Grant Funding Source: NIH‐NIMHD G12MD007582