Effect of Zamzam Water Alone or In Combination with Methadone on Animal Withdrawal Symptoms in Morphine Dependent Rats

Prolong activation of Mu-Opioid receptor will causes adaptation to the downstream system of opioid. This adaptation is believed to be a key factor for tolerance and opioid dependence. This study aimed to investigate the potential of Zamzam water, healing nature water that reported to have high concentration of mineral on alleviating the morphine withdrawal symptoms of morphine-dependent rat. In this experimental study, 50 male Sprague Dawley rats (250–300 g) were randomly divided into five groups of 10 (normal group, untreated group, methadone treated group, Zamzam water treated group, and co-treatment methadone and Zamzam water group). The morphine dependence model was obtained through intraperitoneal (i.p.) injection of morphine (50–75 mg/kg) at increasing doses for 30 days. Morphine dependent rats then were treated with methadone, Zamzam water and co-treatment methadone and Zamzam water for 30 days, respectively. Spontaneous withdrawal symptoms (diarrhea, wet dog shake, body writhing, jumping, teeth chattering) were observed on day one, seven, fourteen, twenty one and thirty of withdrawal. Next, the obtained data were analyzed using SPSS v.11 software, and one way ANOVA followed by Tukey's post statistical tests The data obtained from this animal behaviour observation indicates that the co-treatment methadone and Zamzam water significantly attenuated the spontaneous withdrawal symptoms (diarrhea, wet dog shake) of morphine-dependent rat compared to other groups’ (P < 0.05). This is probably due to the capability of methadone and mineral especially sodium in Zamzam water to prevent downregulation of MOR-1 after chronic morphine administration. We have concluded that co-treatment of methadone and Zamzam water significantly attenuates the spontaneous morphine withdrawal symptoms; Diarrhea and wet dog shake among rats.