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

Evaluation of anti-inflammatory and analgesic activity of the extract and fractions of Astragalus hamosus in animal models

The objective of this study was to evaluate the anti-inflammatory and analgesic activities of the hydro-alcoholic extract of the pods of Astragalus hamosus [HAAH], a plant used in Iranian traditional medicine, and antinociceptive effects of different fractions in animal models. The anti-inflammatory effect was evaluated by the rat paw edema induced by formalin. Also the analgesic effect was examined by the acetic-acid-induced writhing response and hot plate test. The analgesic effects of chloroform, hexane, ethyl acetate and aqueous fractions were evaluated by the hot-plate method. The hydroalcoholic extract of Astragalus hamosus could reduce the edema in a dose-dependent manner [P<0.05]. In the acute phase, the result of 1000 mg/Kg and in the chronic phase, the result of 100 and 300 mg/Kg of the extract were more significant and comparable with the effect of sodium salicylate. Also application of different doses of HAAH had significant anti-nociceptive effects on both animal models. The findings showed that HAAH at doses of 700 and 1000 mg/Kg produced analgesic effects comparable to sodium salicylate. The hexane and ethyl acetate [but not the other fractions] showed significant analgesic activity in hot plate test, when compared to morphine. The results of this study demonstrated the anti-inflammatory and analgesic effects of HAAH extract and hexane and ethyl acetate fractions of the extract in animal models and justify traditional use of this plant in the treatment of pain and inflammatory conditions. More studies to clarify the active components are necessary

Preventive effect of central administration of venlafaxine on morphine physical dependence, nociception, and blood cortisol level in rat

Chronic abuse of opiates induces dependency, but the neurobiological mechanisms of this event remain unclear. The aim of this study was to evaluate the effects of intracerebroventricular of venlafaxine on the morphine dependence and pain perception. A total of 80 adult male rats were divided into two major groups: [1] 40 of them was divided into groups of positive control [morphine dependent] negative control [received saline] and morphine dependent groups under treatment by central administration of venlafaxine at various dosages [25, 50, or 100 microg], after drug treatment total withdrawal index [TWI], latency time of withdrawal syndrome expression and blood cortisol as marker of anxiety were measured and compared with positive control and negative control. [2] Forty rats were grouped in control; indometacin treated [5 mg/kg] and grouped which received central administration of venlafaxine at three doses [25, 50, or 100 microg] and then pain perception and expression was assessed in the writhing test [acetic acid induced abdominal constriction], tail flick, and hot plate test. Central administration of three doses [25, 50, or 100 microg,] of venlafaxine attenuates TWI to 47 +/- 1.2, 38 +/- 1.5, and 23 +/- 1.1 and decrease blood cortisol level to 14 +/- 1, 13.75 +/- 0.5, and 12.5 +/- 0.8, this decreases was significant in comparison with the positive control group [P < 0.05]. Central administration of venlafaxine at mentioned doses significantly attenuates pain response with 37%, 24%, and 20% inhibition in writhing test, 69%, 34%, and 23% inhibition in hot plate test, and 29%, 23%, and 15% inhibition in tail flick test in comparison with control group [P < 0.05]. This study suggested that central administration of venlafaxine attenuated morphine withdrawal index and can be effective in modulation of pain that was induced by morphine dependency

Preventive effects of forced exercise against alcohol-induced physical dependency and reduction of pain perception threshold

Treatment of postabstinence syndrome of alcohol is one of the major strategies of alcoholism treatment. Exercise can be modulated major brain pathways such as a reward system and pain perception centers. The aim of this study was to evaluation the effects of forced exercise in the management of alcohol dependence and pain perception alteration which induced by alcoholism. 72 adult male rats were divided into 2 major groups: [1] 40 of them was divided into groups of positive control [alcohol dependent] negative control and alcohol dependent groups under treatment by forced exercise, diazepam [0.4 mg/kg] and forced exercise in combination with diazepam and alcohol withdrawal signs, and blood cortisols, were measured in this groups. [2] 32 rats were divided into control, alcohol dependent [without treatment], and alcohol-dependent groups under treatment by forced exercise or indometacin [5 mg/kg] and then pain perception was assessed by using writhing test, tail-flick and hot plate test. Forced exercise, diazepam, and their combinations significantly attenuates withdrawal syndrome to 20 +/- 2, 22 +/- 1.3 and 16 +/- 2 and blood cortisol level to 6.8 +/- 1.3, 7.9 +/- 1.2 and 5.8 +/- 1.1, respectively, in comparison with the positive control group [P < 0.05 and P < 0.001]. In alcohol dependent animal under treatment by forced exercise, pain response significantly inhibited with 37%, 57% and 38% decreases in writhing test, hot plate, and tail-flick test, respectively, in comparison with alcohol dependent [without treatment] group [P < 0.05]. This study suggested that forced exercise can be useful as adjunct therapy in alcoholism patient and also can be effective in modulation of pain threshold reduction that was induced by alcohol dependency