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.