title: Oleuropein, chief constituent of olive leaf extract, prevents the development of morphine antinociceptive tolerance through inhibition of morphine-induced L-type calcium channel overexpression.
abstract: It has been shown that blockade of L-type calcium channels could abolish the development of opioid-induced 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 mg/kg, i.p.) for 8 days to induce antinociceptive tolerance. Then OLE (50-200 mg/kg i.g.) and oleuropein (1-10 mg/kg i.p.) were injected concomitantly with morphine. The tail-flick test was used to assess the nociceptive threshold. The dorsal half of the lumbar spinal cord was assayed for the expression of L-type calcium channel using semiquantitative RT-PCR. The results showed that OLE (200 mg/kg) completely prevented morphine tolerance development. In addition, oleuropein in dose of 10 mg/kg, but not in 5 mg/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. 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.
authors.affiliation: Department of Biology, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Zare
authors.forename: Saeed
authors.initials: S
authors.lastname: Esmaeili-Mahani
authors.forename: Mehdi
authors.initials: M
authors.lastname: Abbasnejad
authors.forename: Bahram
authors.initials: B
authors.lastname: Rasoulian
authors.forename: Vahid
authors.initials: V
authors.lastname: Sheibani
authors.forename: Hedayat
authors.initials: H
authors.lastname: Sahraei
authors.forename: Ayat
authors.initials: A
authors.lastname: Kaeidi
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D004361:Drug Tolerance; D057888:Iridoid Glucosides; D039823:Iridoids; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D031658:Olea / Q000737:chemistry; D010147:Pain Measurement; D010936:Plant Extracts / Q000494:pharmacology; D011714:Pyrans / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000701:Analgesics, Opioid; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D057888:Iridoid Glucosides; D039823:Iridoids; D010936:Plant Extracts; D011714:Pyrans; C002769:oleuropein; D009020:Morphine