Effect of aqueous ethanol extract of Hypericum perforatum on naloxane-precipitated opium withdrawal syndrom

Abstract

The aqueous-ethanol extract of the Hypericum perforatum (Hp-Ext.) was studied for its possible effect on Naloxone (NLX)-precipitated Opium withdrawal physical signs in rats. Purified Opium was used to induce dependence in rats using 8 days treatment schedule. The animals received Opium extract orally twice daily at 09:00 hrs and 19:00 hrs starting with initial dose of 80 mg/kg (equivalent to 8 mg/kg morphine) and increasing to 650 mg/kg (equivalent to 65 mg/kg morphine). Withdrawal syndrome was precipitated with NLX (0.25 mg/kg, s/c). Animals were divided into three groups each containing nine rats. Group one served as a control and received opium + saline during opium dependence schedule and the remaining two groups were treatment group, one of which received Hp-Ext (20 mg/kg, p/o) one hour before NLX induced withdrawal and was administered opium + saline through out the dependence protocol and 2nd treated group received opium along with Hp-Ext doses though out the dependence protocol. The spasmolytic and calcium antagonist activities of the plant extract were studied using isolated tissue experiments suspended in the Krebs solution maintained at 37 ?C and aerated with carbogen gas. The results showed a significant decrease in both, NLX-induced Opium withdrawal Jumps and Wet Dog Shakes behavior in chronically treated group (ANOVA; P < 0.05 followed by Dunnet post hoc analysis) but no significant effect was found in the acute treatment group. Interestingly, a significant effect was observed on diarrhea in acute treatment group (ANOVA; p < 0.05, followed by Student Newman Keuls test) but no such effect was seen in the chronically treated group. In a separate study, the plant extract inhibited K+-induced contractions in isolated rabbit jejunum and trachea preparations thus showing spasmolytic effect mediated through calcium antagonist activity. In view of the reported fact that NLX-induced opioid withdrawal signs could be inhibited by calcium antagonists, our results indicate the possibility that the opioid withdrawal ameliorating effect of H. perforatum extract may be at least partly though calcium channel blockade. Acknowledgements: We gratefully acknowledge the help and cooperation for the supply of Opium by Anti Narcotic Force (ANF) Peshawar Division. Financial support of University of Pehsawar is also acknowledged.