N-methyl-D-aspartate (NMDA) receptors are mainly involved in opioid addiction and are highly expressed in the brain reward pathway. Presence of GluN3A subunit in the composition of NMDA receptor decreases conductance of receptor channel. Opioid administration may change the expression pattern of NMDA receptor subunits. Here we have investigated the mRNA expression alterations of GluN3A subunit of the NMDA receptor in the rat brain after acute and chronic morphine administration. Male Wistar rats received chronic intraperitoneal injections of escalating doses of morphine twice daily for 6 days. Control animals received saline instead of morphine with the same protocol. Two other groups received acute single dose of morphine (30 mg/kg) or saline, respectively. The mRNA expression of GluN3A subunit of NMDA receptor in prefrontal cortex, hippocampus, striatum, and nucleus accumbens was evaluated using real-time PCR method. The mRNA expression level of GluN3A subunit was significantly increased (1.5 fold) in prefrontal cortex in chronic morphine administered rats compared to control group. No statistically significant difference was observed between control and chronic morphine treated rats in other sites of the brain. In acute morphine administered animals, no significant difference was observed in GluN3A subunit expression in evaluated sites of the brain compared to the control group. It is concluded that chronic morphine administration leads to the up-regulation of GluN3A subunit of NMDA receptor in prefrontal cortex. Involvement of this alteration in features of opioid addiction needs to be further studies in the future.

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