{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:14:42Z","timestamp":1791918882569,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2012,3,15]],"date-time":"2012-03-15T00:00:00Z","timestamp":1331769600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:p>It has been shown that blockade of L\u2010type calcium channels could abolish the development of opioid\u2010induced antinociceptive tolerance. Here, the antitolerant effects of olive leaf extract (OLE) and its main component, oleuropein, which have a calcium channel blocker property were determined. Adult male Wistar rats were injected with morphine (20\u2009mg\/kg, i.p.) for 8\u2009days to induce antinociceptive tolerance. Then OLE (50\u2013200\u2009mg\/kg i.g.) and oleuropein (1\u201310\u2009mg\/kg\u2009i.p.) were injected concomitantly with morphine. The tail\u2010flick test was used to assess the nociceptive threshold. The dorsal half of the lumbar spinal cord was assayed for the expression of L\u2010type calcium channel using semiquantitative RT\u2010PCR.<\/jats:p><jats:p>The results showed that OLE (200\u2009mg\/kg) completely prevented morphine tolerance development. In addition, oleuropein in dose of 10\u2009mg\/kg, but not in 5\u2009mg\/kg, prevented the development of morphine antinociceptive tolerance. In addition, a significant increase in the mRNA levels of calcium channel (43.9%) was observed in the lumbar spinal cord of tolerant animals, which was reversed by effective of dose OLE.<\/jats:p><jats:p>In conclusion, the results indicate that olive leaf extract has a potential antitolerant property against the chronic usage of morphine and that its main component, oleuropein, is responsible for such effect. Copyright \u00a9 2012 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/ptr.4634","type":"journal-article","created":{"date-parts":[[2012,3,16]],"date-time":"2012-03-16T03:14:53Z","timestamp":1331867693000},"page":"1731-1737","source":"Crossref","is-referenced-by-count":26,"title":["Oleuropein, Chief Constituent of Olive Leaf Extract, Prevents the Development of Morphine Antinociceptive Tolerance through Inhibition of Morphine\u2010induced L\u2010type Calcium Channel Overexpression"],"prefix":"10.1002","volume":"26","author":[{"given":"Leila","family":"Zare","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Sciences Shahid Bahonar University of Kerman Kerman Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed","family":"Esmaeili\u2010Mahani","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Sciences Shahid Bahonar University of Kerman Kerman Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Abbasnejad","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Sciences Shahid Bahonar University of Kerman Kerman Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahram","family":"Rasoulian","sequence":"additional","affiliation":[{"name":"Razi Herbal Medicines Research Center Lorestan University of Medical Sciences Khoramabad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahid","family":"Sheibani","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neuroscience, Kerman Neuroscience Research Center (KNRC) Kerman University of Medical Sciences Kerman Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedayat","family":"Sahraei","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center Baqiyatallah University of Medical Sciences Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayat","family":"Kaeidi","sequence":"additional","affiliation":[{"name":"Razi Herbal Medicines Research Center Lorestan University of Medical Sciences Khoramabad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,3,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-010-0215-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02253536"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf025540p"},{"key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/S0022-3565(25)03823-6","article-title":"A method of determining loss of pain sensation","volume":"27","author":"D'Amour FE","year":"1941","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(00)00249-9"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1016\/S0022-3565(25)10714-3","article-title":"Regulation of dihydropyridine\u2010sensitive Ca2+ channels during opioid tolerance and supersensitivity in rats","volume":"274","author":"Diaz A","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000184253.49849.B0"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(02)01736-8"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.07.019"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2009.00248.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2007.10.012"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2005.03.004"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2010.08.013"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/0963748031000136306"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/09637480500539420"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.npep.2010.02.004"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2007.09.003"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1556\/AChrom.22.2010.1.10"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(99)00469-0"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000087658"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11746-009-1517-x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biortech.2009.12.052"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1251\/bpo20"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.02.066"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(98)00373-2"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2010.06.007"},{"key":"e_1_2_7_28_1","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/S0026-895X(25)08594-3","article-title":"Ca2+ channel and adenylyl cyclase modulation by cloned mu\u2010opioid receptors in GH3 cells","volume":"47","author":"Piros ET","year":"1995","journal-title":"Mol Pharmacol"},{"key":"e_1_2_7_29_1","first-page":"539","article-title":"Effects of verbascoside and luteolin on oxidative damage in brain of heroin treated mice","volume":"60","author":"Qiusheng Z","year":"2005","journal-title":"Pharmazie"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(88)90488-8"},{"key":"e_1_2_7_31_1","first-page":"219","article-title":"Nimodipine is more effective than nifedipine in attenuating morphine tolerance on chronic co\u2010administration in the rat tail\u2010flick test","volume":"46","author":"Ray SB","year":"2008","journal-title":"Indian J Exp Biol"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2008.11.005"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(94)90192-9"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2008.08.018"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.FP0070885"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(98)00168-3"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2008.10.038"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(91)90241-3"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200508000-00011"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(83)90201-4"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fptr.4634","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fptr.4634","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.4634","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T08:08:29Z","timestamp":1742717309000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.4634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3,15]]},"references-count":39,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2012,11]]}},"alternative-id":["10.1002\/ptr.4634"],"URL":"https:\/\/doi.org\/10.1002\/ptr.4634","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,3,15]]}}}