Attenuation of withdrawal signs, blood cortisol, and glucose level with various dosage regimens of morphine after precipitated withdrawal syndrome in mice

Morphine withdrawal usually results in unsuccessful outcomes. Despite partial benefits from alternative substances such as methadone, its use may not lead to the desired result due to the lack of mental tranquility during the withdrawal period. In this study, by means of an animal model, morphine itself was used to manage morphine dependence. Forty mice were divided into 5 groups, in which 4 groups became dependent by increasing daily doses of morphine for 7 days [15-45 mg/kg]. Afterwards, the animals received morphine for 14 days by either of the following regimens: - Once daily 45 mg/kg [positive controls]. - Increasing the interval [each time 6 hours longer than the previous interval]. - Irregular interval in every 36, 12 and 24 hours until the 21[th] day. - 12, 24, 36 hours decreasing doses [each time 2.5 mg/kg less than the former dosage]. Negative controls received saline solution only. On day 22, total withdrawal index [TWI] was determined by injecting 3 mg/kg of naloxone. Thereafter, blood samples were taken for the measurement of cortisol and glucose levels. TWI significantly decreased in all test groups in comparison with the positive control animals [P<0.001]. Cortisol levels significantly decreased when either the dosage or the administration frequencies were decreased on a regular and gradual basis [P<0.005]. Blood glucose levels significantly decreased in animals that received decreasing doses of morphine [P<0.005]. This study suggests that no other measures may be required in clinical practice except for changing the dosage regimen of morphine for the cessation of self-administration

Reduction of kidney damage by supplementation of vitamins C and E in rats with deoxycorticosterone-salt-induced hypertension

We assessed whether cosupplementation of vitamins C and E has additive beneficial effects on reducing the kidney damage and attenuation of the arterial pressure elevation compared to administration of either vitamin C or vitamin E alone in deoxycorticosterone acetate-salt-induced hypertension. Forty rats were divided into 4 study groups and 1 sham-operated group. Unilateral nephrectomy was carried out in the study groups and hypertension was induced by deoxycorticosterone injection and 1% sodium chloride and 0.2% potassium chloride added to the drinking water. Vitamins C and E [200 mg/kg/day] or combination of them were administered with DOCA-salt for 4 weeks in 3 study groups. The effects of DOCA and salt and treatment with vitamins were compared in terms of blood pressure, urinary protein excretion, antioxidant activity of the kidneys, and renal histological changes. Four weeks of supplementations of vitamins C, vitamin E, and both in the DOCA-salt-treated rats had comparable significant effects in decreasing systolic blood pressure. Urinary protein excretion and histological damage did not significantly change with the combination therapy of vitamins C and E compared to the vitamin C or E alone. The renal levels of glutathione and ferric reducing/antioxidant power in combination therapy group were similar to the two other treatment groups and were significantly higher than non-treated group. Co-administration of vitamin C and E does not have an additive beneficial effect on reducing the kidney damage and hypertension compared to either vitamin C or E alone in DOCA-salt-induced hypertension