Expression of NR3B but not NR2D subunit of NMDA receptor in human blood lymphocytes can serve as a suitable peripheral marker for opioid addiction studies.

Glutamate is critically involved in opioid addiction. It has been suggested that neurotransmitter receptors expression in peripheral blood lymphocytes may reflect brain status. In the present study, using Real-time PCR, the mRNA expression of NR2D and NR3B subunits of NMDA glutamate receptor has been investigated in peripheral blood lymphocytes of four groups each comprising of 25 male individuals: opioid addicts, methadone maintained patients, long-term abstinent former opioid addicts, and non-addicted control subjects. We found that NR2D subunit mRNA expression was not changed in all three test groups in comparison to control subjects. However, the NR3B mRNA expression was significantly up-regulated by the factors 9.11 (P<0.001), 10.07 (P<0.001) and 4.08 (P<0.05) in abstinent, addicted and methadone maintained subjects, respectively relative to control group. As a conclusion, our data indicate that the transcriptional level of the NR2D subunit of NMDA receptor is not regulated by chronic opioid addiction. However, it seems that the over-expression of NR3B subunit of NMDA receptor is a long lasting result of opioid abuse. In addition, considerable decrease in the up-regulated state of the NR3B subunit by methadone may represent another benefit of methadone therapy for opioid addicts and may serve as a suitable marker to evaluate the successfulness of therapy.