The Effects of Ethanolic Extract of Dill (Anethum graveolens)) on Morphine Withdrawal Symptoms in Addicted Male NMRI Rats

Background & aim: Medicinal herbs with natural materials can be effective and have fewer side effects than drugs with chemical composition in reducing withdrawal symptoms and are more effective in treating addiction. In recent years, anti-inflammatory, analgesic and anti-anxiety effects of Dill has been reported. The purpose of this study was to determine the effect of Dill ethanol extract on some withdrawal syndrome behaviors such as jumping, standing, climbing in male mice addicted to morphine. Methods: The present experimental study was conducted on 21 male NMRI mice with weighting 25 to 30 gr. Animals were divided into three groups: Group 1 received saline + naloxone (SN),&nbsp; group 2 received morphine + saline + naloxone (MSN) and the third group received&nbsp;&nbsp; morphine + ethanol extract of dill (500 mg kg ip) + naloxone (MDN) respectively. Simultaneous with the injection of morphine, the dill extract was injected at the same time. In order to induce the development of morphine dependence, the mice received increasing doses of morphine (10, 20, 30, and 40 mg) during four days for ten times, respectively. To induce the withdrawal symptom, two hours after the last injection of morphine, naloxone at a dose of 5 mg kg was injected intraperitoneally. Two hours after the last injection of morphine, naloxone at a dose of 5 mg/kg was injected intraperitoneally. Jumping, standing on both feet and climbing the walls were counted during 30 minutes. The data were analyzed using the software Graph Pad prism. Results: The results showed that the ethanol extract of plant significantly reduces the number of jumping due to naloxone injection in the addicted rats (p <0.001), but in the rearing behaviors and climb the walls of the container, a significant difference was observed with morphine. Conclusions: The findings suggested that the Dill Ethanolic extract can decrease the jumping number due to Naloxone-induced effect.&nbsp; Therefore, Dill Ethanolic extract may have an impact in reducing of withdrawal induction by morphine

The Effect of Morphine Dependency on Serum Levels of Trace Elements (Copper, Zinc, and Manganese) in Male Rats

Background & aim: In some studies, changes in trace elements of abuse of addictive substances have been mentioned. Due to the effects of trace elements on the immune system and their effects on susceptibility to infectious agents, the purpose of this study was to investigate the effect(s) of morphine dependency on the concentration of trace elements (copper, zinc and manganese) levels in serum of rats. Methods: In the present study, twenty-four adult male Wistar rats were randomly divided into two groups of receiving morphine (experimental) and control one. In the experimental group, morphine were injected subcutaneously twice daily for thirty days. Morphine dose on the first day was 10 mg/ml/kg daily and increased 2 mg/kg daily until it reached a maximum of 68 mg/kg. Instead of morphine, the control group received 1 ml/kg of normal saline for 30 days. Withdrawal syndrome in morphine-dependent groups and the control group were injected with 4 mg/kg naloxone in four animals from each group and then evaluated. Serum concentrations of zinc, copper and manganese were determined by spectrometer coupled plasma optical emission detector. Data were analyzed by Student's t test. Results: Serum concentrations of manganese in morphine-dependent group compared with the control group was significantly lower (p<0.05), whereas serum zinc and copper concentrations were significantly higher than the control group (p<0.05). Results showed a significant increase in serum copper and zinc concentrations and decrease in serum manganese level in morphine dependent rats. Conclusion: Dependence to morphine may be affecting the status of trace elements in serum of male rats

The Effects of Testosterone and Gonadectomy Conditions on Nociception and Their Effect on Morphine-Induced Analgesia in Male Mice, Using the formalin test

Introduction & Objective: There are too many disagreements about the effects of gender and sex hormones on the behavioral responses to noxious stimuli and morphine analgesia. The purpose of this study was to determine the different effects of testosterone and gonadectomy conditions on pain and morphine-induced analgesia, using the formalin test. Materials & Methods: The present study was conducted at Razi University, in Kermanshah. Sixty three male NMRI mice were divided into nine groups (n=7). The effects of gonadectomy and testosterone on responses to noxious stimuli were evaluated in five groups (G1 to G5). The effects of these factors on morphine-induced analgesia were investigated in other groups (G6 to G9). According to grouping, each group received normal saline, testosterone, testosterone solvent or morphine and some groups were also gonadectomized and separately received these agents. Finally, the formalin test was taken from all groups. Data were statistically analyzed by one-way ANOVA. Results: The results showed that the response to the painful stimuli had no significant difference in 5 minutes (acute pain) in all groups. Testosterone increased the response to the noxious stimuli in sub acute pain (10-30 minutes) and chronic phase (15-60 minutes) stages. This increase was significant in the group receiving testosterone compared with the gonadectomized group in both stages. In the presence of morphine, there were no significant differences in response to painful stimulus in 5 minutes (acute pain) in all groups. But testosterone in the presence of morphine caused an increased in pain score in sub acute pain (10-30 minutes) and chronic phase (15-60 minutes) stages. Conclusion: Testosterone increased the response to the painful stimuli in sub acute and chronic pain stages. Testosterone also reduced morphine-induced analgesia in peripheral and chronic pain stages in mice