NMDA receptor subunits change in the prefrontal cortex of pure-opioid and multi-drug abusers: a post-mortem study

Abstract

Addiction is a chronic relapsing disorder and is one of the most important issues in the world. Changing the level of neurotransmitters and the activities of their receptors, play a major role in the pathophysiology of substance abuse disorders. It is well-established that N-methyl-D-aspartate receptors (NMDARs) play a significant role in the molecular basis of addiction. NMDAR has two obligatory GluN1 and two regionally localized GluN2 subunits. This study investigated changes in the protein level of GluN1, GluN2A, and GluN2B in the prefrontal cortex of drug abusers. The medial prefrontal cortex (mPFC), lateral prefrontal cortex (lPFC), and orbitofrontal cortex (OFC) were dissected from the brain of 101 drug addicts brains and were compared with the brains of non-addicts (N = 13). Western blotting technique was used to show the alteration in NMDAR subunits level. Data obtained using Western blotting technique showed a significant increase in the level of GluN1 and GluN2B, but not in GluN2A subunits in all the three regions (mPFC, lPFC, and OFC) of men whom suffered from addiction as compared to the appropriate controls. These findings showed a novel role for GluN1, GluN2B subunits, rather than the GluN2A subunit of NMDARs, in the pathophysiology of addiction and suggested their role in the drug-induced plasticity of NMDARs.

Identification and Characterization of Biomarkers and Their Role in Opioid Addiction by Integrated Bioinformatics Analysis

“…induced by NMDA receptor blockade in neonatal rats (Sutton and Schuman, 2006;Hoogenraad et al, 2007;Huang et al, 2017). Of particular interest, immunoblotting data reveals a marked increase in GluN1 and GluN2B expression in three regions (medial prefrontal cortex mPFC, Lateral prefrontal cortex LPFC, and orbitofrontal cortex OFC) in men suffering from opioid addiction (Daneshparvar et al, 2019), suggesting that ADCY9 may also be involved in changes to NMDA receptors in opioid addiction. These changes may lead to behavioral sensitization and the formation of addictive memory.…”

Mechanism of opioid addiction and its intervention therapy: Focusing on the reward circuitry and mu‐opioid receptor

“…A postmortem study found that in opioid drug abusers, the expression of the GluN1 and GluN2B but not the GluN2A subunits of the NMDA receptors was increased in both the mPFC and the lateral PFC. 209 Moreover, further animal studies demonstrated that chronic morphine administration could significantly increase the total dendrite length and dendritic complexity of both PV interneurons and somatostatin interneurons in the mPFC. 210 Another study showed that chronic cocaine administration increased the level of MORs mRNA in the PFC.…”

Narcotic Addiction in Failed Back Surgery Syndrome

“…Many neurotransmitters are involved in drug addiction; one being glutamate. Glutamate is the major excitatory neurotransmitter in the brain that modulates the activity of the dopaminergic system 51 . There are two types of glutamate receptors: ionotropic receptors and metabotropic receptors.…”

“…There are two types of glutamate receptors: ionotropic receptors and metabotropic receptors. The N-methyl-D-aspartate (NMDA) receptor is an ionotropic receptor for glutamate and plays a key role in addiction 51 – 53 . When NMDA receptors are activated, they exhibit long-lasting electrical currents that significantly increase calcium permeability 54 .…”

“…These memories enable drug-related stimuli to have powerful control over future behaviors and result in promoting addiction 54 . Daneshparvar et al 55 found that NMDA receptor subunits (GluN1 and GluN2B) were significantly increased in the prefrontal cortex of drug abusers 51 . Mayer et al discovered that long-term morphine use leads to excessive activation of NMDA receptors via the stimulation of MOR 56 .…”