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Background: Sodium ion is an essential ion that is implicated in many physiological functions. Recently, sodium ion was reported to facilitate the activation of Mu-Opioid Receptor (MOR) by binding at the allosteric site of the MOR. Zamzam water is water originated from Mecca. Couple of studies proved that Zamzam water has the therapeutic effect owing to its mineral. In this study, we want to determine the ion concentration of Zamzam water and then to investigate the effects of Zamzam water and co-treatment with methadone on the regulation of MOR-1gene after chronic morphine administration. Materials and Methods: Zamzam water, tap water and normal mineral water were analyzed using Ion chromatography. Meanwhile, in animal study, 50 male Sprague Dawley rats were randomly divided into five groups. All group of rat were made dependence on morphine using intraperitoneal injection except for normal group. Morphine dependent rats then were treated with methadone, Zamzam water and co-treatment methadone with Zamzam water for thirty days, respectively. The Ventral Tegmental Area (VTA) of rat’s brain was dissected and subjected to real-time quantitative RT-PCR to determine the regulation of MOR-1 gene expression. The obtained data were analyzed using SPSS v.11 software, and one-way ANOVA followed by Tukey’s Post-test. Results: The data obtained showed that Zamzam water is significantly high in ion concentration compared to tap water and normal mineral water. Besides, the result from gene expression analysis showed co-treatment Zamzam water and methadone significantly prevented the downregulation of MOR as compared to methadone and Zamzam water treatment alone (P<0.05). A possible explanation for this might be due to the presence of sodium ion in Zamzam water which activate MOR then promote the endocytosis of the MOR. Conclusion: We concluded that co-treatment of methadone and Zamzam water significantly prevented downregulation of MOR-1 gene by promoting the endocytosis of MOR.

EFFECTS OF ZAMZAM WATER AND METHADONE ON THE EXPRESSION OF MU-OPIOID RECEPTOR-1 GENE IN MORPHINE-DEPENDENT RATS AFTER CHRONIC MORPHINE ADMINISTRATION