Evaluation of the Effects of Chronic Administration of Citrus aurantium Essential Oil on the Development of Tolerance and Dependence to Morphine
Background: Long-term exposure to opioids may lead to physical dependence and tolerance. The purpose of this study was to investigate the effects of Citrus aurantium essential oil (CEO) on the morphine-induced tolerance and dependence. Methods: To evaluate morphine tolerance, the experiments were ca...
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| Format: | Article |
| Language: | English |
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Tabriz University of Medical Sciences
2019-03-01
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| Series: | Pharmaceutical Sciences |
| Subjects: | |
| Online Access: | https://ps.tbzmed.ac.ir/PDF/PHARM_1070_20180120095210 |
| _version_ | 1818931851828396032 |
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| author | Alireza Parvizpur Kosar Parnian Sama Samankan Fatemeh Fathiazad Mohammad Charkhpour |
| author_facet | Alireza Parvizpur Kosar Parnian Sama Samankan Fatemeh Fathiazad Mohammad Charkhpour |
| author_sort | Alireza Parvizpur |
| collection | DOAJ |
| description | Background: Long-term exposure to opioids may lead to physical dependence and tolerance. The purpose of this study was to investigate the effects of Citrus aurantium essential oil (CEO) on the morphine-induced tolerance and dependence. Methods: To evaluate morphine tolerance, the experiments were carried out in 6 rat groups (n=8) in the weight range of 225-275 g. The control group received morphine (10 mg/kg/day) and the test groups received morphine with the different doses of essential oil (CEO 20, 40 and 80 mg/kg/day) or 4 mL/kg of essential oil vehicle (KolliphorÒ HS15 30% in normal saline that adjusted in pH=7.4 with phosphate buffer) intraperitoneally. The hot-plate test was carried out every other day, 90 minutes after the injections. To examine morphine withdrawal, male Wistar rats were divided into seven groups (n=8) randomly, including: morphine sulphate, CEO (20, 40 and 80 mg/kg) + morphine, vehicle of CEO + morphine. The rats were rendered morphine-dependent by injection of additive doses of morphine subcutaneously for 9 days. The procedure of the morphine administration was as following protocol: day1: 5 mg/kg/12h, day 2 and 3: 10 mg/kg/12h, day 4 and 5: 15 mg/kg/12h, day 6 and 7: 20 mg/kg/12h and day 8 and 9: 25 mg/kg/12h. In the 9th day, 2 hours after the last dose of morphine, naloxone (4 mg/kg) was injected intraperitoneally. Some withdrawal behaviors were counted for 60 minutes. Results: Morphine tolerance was completed after 5 days in the control group. The vehicle group showed tolerance on the 9th day (p-value=0.991), 20mg group in the 13th day (p-value to control=0.010, to vehicle=0.049), 40 mg group on the 15th day (p-value to control and vehicle<0.001) and 80 mg group on the 13th day (p-value to control= 0.001, to vehicle= 0.007). The results showed that CEO could reduce the morphine withdrawal syndrome and total withdrawal score (TWS). Intraperitoneally injection of CEO in two doses (40 mg/kg with p<0.001 and 80 mg/kg with p<0.01) significantly reduced the TWS in comparison to the morphine+vehicle treated group. Conclusion: The results indicated that chronic administration of C. aurantium essential oil extracted had beneficial effects in reducing morphine withdrawal syndrome and could significantly delay tolerance to morphine. |
| first_indexed | 2024-12-20T04:23:10Z |
| format | Article |
| id | doaj.art-594fb2eace744786b94508487721849e |
| institution | Directory Open Access Journal |
| issn | 1735-403X 2383-2886 |
| language | English |
| last_indexed | 2024-12-20T04:23:10Z |
| publishDate | 2019-03-01 |
| publisher | Tabriz University of Medical Sciences |
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| series | Pharmaceutical Sciences |
| spelling | doaj.art-594fb2eace744786b94508487721849e2022-12-21T19:53:35ZengTabriz University of Medical SciencesPharmaceutical Sciences1735-403X2383-28862019-03-01251172310.15171/PS.2019.3PHARM_1070_20180120095210Evaluation of the Effects of Chronic Administration of Citrus aurantium Essential Oil on the Development of Tolerance and Dependence to MorphineAlireza Parvizpur0Kosar Parnian1Sama Samankan2Fatemeh Fathiazad3Mohammad Charkhpour4Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.Department of Pharmacognosy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.Background: Long-term exposure to opioids may lead to physical dependence and tolerance. The purpose of this study was to investigate the effects of Citrus aurantium essential oil (CEO) on the morphine-induced tolerance and dependence. Methods: To evaluate morphine tolerance, the experiments were carried out in 6 rat groups (n=8) in the weight range of 225-275 g. The control group received morphine (10 mg/kg/day) and the test groups received morphine with the different doses of essential oil (CEO 20, 40 and 80 mg/kg/day) or 4 mL/kg of essential oil vehicle (KolliphorÒ HS15 30% in normal saline that adjusted in pH=7.4 with phosphate buffer) intraperitoneally. The hot-plate test was carried out every other day, 90 minutes after the injections. To examine morphine withdrawal, male Wistar rats were divided into seven groups (n=8) randomly, including: morphine sulphate, CEO (20, 40 and 80 mg/kg) + morphine, vehicle of CEO + morphine. The rats were rendered morphine-dependent by injection of additive doses of morphine subcutaneously for 9 days. The procedure of the morphine administration was as following protocol: day1: 5 mg/kg/12h, day 2 and 3: 10 mg/kg/12h, day 4 and 5: 15 mg/kg/12h, day 6 and 7: 20 mg/kg/12h and day 8 and 9: 25 mg/kg/12h. In the 9th day, 2 hours after the last dose of morphine, naloxone (4 mg/kg) was injected intraperitoneally. Some withdrawal behaviors were counted for 60 minutes. Results: Morphine tolerance was completed after 5 days in the control group. The vehicle group showed tolerance on the 9th day (p-value=0.991), 20mg group in the 13th day (p-value to control=0.010, to vehicle=0.049), 40 mg group on the 15th day (p-value to control and vehicle<0.001) and 80 mg group on the 13th day (p-value to control= 0.001, to vehicle= 0.007). The results showed that CEO could reduce the morphine withdrawal syndrome and total withdrawal score (TWS). Intraperitoneally injection of CEO in two doses (40 mg/kg with p<0.001 and 80 mg/kg with p<0.01) significantly reduced the TWS in comparison to the morphine+vehicle treated group. Conclusion: The results indicated that chronic administration of C. aurantium essential oil extracted had beneficial effects in reducing morphine withdrawal syndrome and could significantly delay tolerance to morphine.https://ps.tbzmed.ac.ir/PDF/PHARM_1070_20180120095210MorphineDependenceToleranceWithdrawalCitrus aurantium |
| spellingShingle | Alireza Parvizpur Kosar Parnian Sama Samankan Fatemeh Fathiazad Mohammad Charkhpour Evaluation of the Effects of Chronic Administration of Citrus aurantium Essential Oil on the Development of Tolerance and Dependence to Morphine Pharmaceutical Sciences Morphine Dependence Tolerance Withdrawal Citrus aurantium |
| title | Evaluation of the Effects of Chronic Administration of Citrus aurantium Essential Oil on the Development of Tolerance and Dependence to Morphine |
| title_full | Evaluation of the Effects of Chronic Administration of Citrus aurantium Essential Oil on the Development of Tolerance and Dependence to Morphine |
| title_fullStr | Evaluation of the Effects of Chronic Administration of Citrus aurantium Essential Oil on the Development of Tolerance and Dependence to Morphine |
| title_full_unstemmed | Evaluation of the Effects of Chronic Administration of Citrus aurantium Essential Oil on the Development of Tolerance and Dependence to Morphine |
| title_short | Evaluation of the Effects of Chronic Administration of Citrus aurantium Essential Oil on the Development of Tolerance and Dependence to Morphine |
| title_sort | evaluation of the effects of chronic administration of citrus aurantium essential oil on the development of tolerance and dependence to morphine |
| topic | Morphine Dependence Tolerance Withdrawal Citrus aurantium |
| url | https://ps.tbzmed.ac.ir/PDF/PHARM_1070_20180120095210 |
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