The Effect of Memantine on the Expression of Dopamine Receptors in the Striatum of Male Rats With Morphine Addiction

Background and Objectives: Studies have indicated that the chronic use of morphine can result in physical and psychological dependence. Morphine dependence is associated with several cellular and molecular alterations in the mesocorticolimbic system, and striatal dopamine signaling is involved in this process. In the present study, we aim to investigate possible alterations in the level of dopamine receptors DRD2 and DRD4 in the striatum of male rats following chronic oral administration of morphine and assess the effect of subcutaneous injection of memantine on morphine-induced effects. Methods: In this experimental study, 16 male Wistar rats were randomly divided into four groups: Control, morphine, memantine, and morphine+memantine. The morphine group received increasing doses of morphine (0.1-0.4 mg/kg) via their drinking water for 21 consecutive days. The memantine groups, after receiving distilled water without morphine for 21 days, received a subcutaneous injection of 5 mg memantine. The morphine memantine group received 5 mg of memantine subcutaneously on day 21 and 30 minutes after the last oral administration of morphine. After collecting striatum tissue, dopamine receptor levels were evaluated by the western blotting method. Results: The chronic use of morphine increased the levels of DRD2 and DRD4 compared to the controls. Memantine administration also increased the level of these receptors compared to the controls. In addition, the expression of DRD2 and DRD4 increased in the morphine+ memantine group compared to the memantine group. Conclusion: Morphine affects the expression of dopamine receptors in the striatum. Treatment with memantine can increases dopamine receptors’ expression.