Oleuropein,Chief Constituent of Olive Leaf Extract,Prevents the Development of Morphine Antinociceptive Tolerance through Inhibition of Morphine‐induced L‐type Calcium Channel Overexpression

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. Copyright © 2012 John Wiley & Sons, Ltd.