Abstract

Regarding the proven anticonvulsant effect of Zhumeria majdae essential oil (ZMEO) in previous studies we were prompted to investigate the ZMEO effects on the tolerance to the anticonvulsant effects of morphine and the morphine withdrawal syndrome. Tolerance to the morphine anticonvulsant effect was induced in mice by subcutaneous injection of 2.5 mg/kg of morphine for 4 days. Subsequent doses of ZMEO (20 mg/kg) were used to study the expression and development of morphine tolerance. Clonidine was used as the standard drug to inhibit the morphine withdrawal syndrome symptoms. To study the ZMEO effect on withdrawal syndrome, mice received appropriate morphine values for 4 days and on the fifth day, 60 min before administration of naloxone. The effective dose of ZMEO was determined and the number of jumps, stands and changes in the dry stool weight, as symptoms of withdrawal syndrome were evaluated. The dose of 20 mg/kg of ZMEO decreased the tolerance in development and expression groups significantly. Counting the number of jumping, standing and defecation were assessed 30 min after morphine and 1 h after the vehicle and clonidine. The dose of 40 mg/kg ZMEO decreased all the signs of withdrawal syndrome significantly. ZMEO was analyzed by GC/MS and linalool (53.1%) and camphor (23.8%) were characterized as the main components. The results suggest that ZMEO possesses constituent(s) that have activity against tolerance to the anticonvulsant effects of morphine and the morphine withdrawal symptoms.

Highlights

  • Zumeria majdae Rech. f. & Wendelbo (Lamiaceae) is an endemic plant to the south of Iran and only grows wild just in the heights of Genow Mountains in Northern Bandar Abbas (Rechinger, 1989)

  • The results suggest that Zhumeria majdae essential oil (ZMEO) possesses constituent(s) that have activity against tolerance to the anticonvulsant effects of morphine and the morphine withdrawal symptoms

  • Effect of different doses of ZMEO on the clonic seizure threshold induced by PTZ

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Summary

Introduction

Zumeria majdae Rech. f. & Wendelbo (Lamiaceae) is an endemic plant to the south of Iran and only grows wild just in the heights of Genow Mountains in Northern Bandar Abbas (Rechinger, 1989). The analgesic, anti-inflammatory, antibacterial, anti-leishmania, anti-malaria and antiseizure effects of this plant have been previously proven (Peana et al, 2003; Linck et al, 2009; Elisabetsky et al, 1999; Moein et al, 2008; Hosseinzadeh et al, 2012). Many studies have shown the effective role of linalool in reducing morphine tolerance and dependence (Hosseinzadeh et al, 2012; Peana et al, 2006; Haghparast et al, 2008). Studies have shown the linalool inhibitory effects on the adenylate cyclase enzyme and intracellular mechanisms in inhibiting action on the central nervous system. In 2008, it was shown that linalool affects the morphine tolerance and dependence by suppressing production of NO (Nitric Oxide) (Haghparast et al, 2008). Linalool regulates a wide range of neurotransmitter and conductive systems such as opioid, dopaminergic, Muscarinic and adenosine receptors as well as KATP canals (K Adenosine Tri Phosphate channel) (Hosseinzadeh et al, 2012)

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