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

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.

Alteration of dopamine receptors subtypes in the brain of opioid abusers: A postmortem study in Iran.

Dopamine is the most important neurotransmitter which is involved in reward and addiction. Repeated drug exposure can induce some adaptive changes in the molecular and cellular function of the mesolimbic dopaminergic system. Since the essential role of dopamine in the pathophysiology of drug addiction is proven, the changes in dopamine receptors level in the brain of opioid abusers and matched control subjects were investigated. Fifty-six opioid abusers and thirteen control subjects were obtained from Legal Medicine Center. The cause of death and the postmortem interval were determined by forensic pathologists. mRNA expression and protein level of dopamine receptors in the ventral tegmental area (VTA), nucleus accumbens (NAC) and amygdala were assessed. The mRNA and protein level of DRD1 increased in the VTA, NAC and amygdala of opioid abusers. DRD2 protein level increased in the VTA, NAC and amygdala of opioid abusers when compared with the control. DRD3 level decreased in all the brain regions except in the amygdala of opioid abusers in comparison with the control group. DRD4 mRNA level increased only in the amygdala of opioid abusers. There were no significant changes in the protein and mRNA levels of DRD4 in the VTA and NAC. In mRNA and protein level of DRD5, it followed the same pattern like DRD1. The current data suggest that adaptive changes in mRNA and protein level of dopamine receptors occurred in the brain of opioid abusers and the variations depended on the brain region.