The Role Of NMDA Receptors In Tolerance And Dependence To The Morphine In The Striatum And The Prefrontal Cortex Of Rat Brain

Introduction: Previous researches have proposed a change in N-Methyl-D-Aspartate (NMDA) receptors during tolerance and dependence to the morphine. Aim: Given the role of glutamate and its receptors in the mesocorticolimbic region including NMDA receptors in opioid addiction, in this study after induction of morphine dependence in male wistar rats, changes in gene expression of NR1 subunit of NMDA receptors, the main subunit of these receptors, in the striatum and the prefrontal cortex of rat brain were examined. Material and Methods: For induction of morphine dependence, a dose of 10 mg/kg of morphine was administrated intraperitoneally for 7 consecutive days. Control group received saline for 7 days. Tolerance to the morphine was examined by a hot plate test of analgesia, 1 day after withdrawal. A semi-quantative RT-PCR was used for evaluating gene expression in different periods after withdrawal. Results: The results showed that the level of mRNA of NR1 in the striatum on day 1 after morphine withdrawal was significantly increased, while in the prefrontal cortex was significantly decreased. On the other interval times of 3, 7, 14 and 21 days after withdrawal, in the two areas compared with control group demonstrated no significant change, and almost returned to the basal level.

Morphine, NMDAR, Striatum, Prefrontal cortex