Metabolic Brain Disease

, Volume 33, Issue 3, pp 939–948 | Cite as

Anticonvulsive effects of endocannabinoids; an investigation to determine the role of regulatory components of endocannabinoid metabolism in the Pentylenetetrazol induced tonic- clonic seizures

  • Parisa Zareie
  • Mehdi Sadegh
  • Mohammad Reza Palizvan
  • Homeira Moradi-Chameh
Original Article
  • 90 Downloads

Abstract

2-Arachidonoylglycerol (2-AG) and anandamide are two major endocannabinoids produced, released and eliminated by metabolic pathways. Anticonvulsive effect of 2-AG and CB1 receptor is well-established. Herein, we designed to investigate the anticonvulsive influence of key components of the 2-AG and anandamide metabolism. Tonic-clonic seizures were induced by an injection of Pentylenetetrazol (80 mg/kg, i.p.) in adult male Wistar rats. Delay and duration for the seizure stages were considered for analysis. Monoacylglycerol lipase blocker (JJKK048; 1 mg/kg) or alpha/beta hydroxylase domain 6 blocker (WWL70; 5 mg/kg) were administrated alone or with 2-AG to evaluate the anticonvulsive potential of these enzymes. To determine the CB1 receptor involvement, its blocker (MJ15; 3 mg/kg) was administrated associated with JJKK048 or WWL70. To assess anandamide anticonvulsive effect, anandamide membrane transporter blocker (LY21813240; 2.5 mg/kg) was used alone or associated with MJ15. Also, fatty acid amide hydrolase blocker (URB597; 1 mg/kg; to prevent intracellular anandamide hydrolysis) were used alone or with AMG21629 (transient receptor potential vanilloid; TRPV1 antagonist; 3 mg/kg). All compounds were dissolved in DMSO and injected i.p., before the Pentylenetetrazol. Both JJKK048 and WWL70 revealed anticonvulsive effect. Anticonvulsive effect of JJKK048 but not WWL70 was CB1 receptor dependent. LY2183240 showed CB1 receptor dependent anticonvulsive effect. However, URB597 revealed a TRPV1 dependent proconvulsive effect. It seems extracellular accumulation of 2-AG or anandamide has anticonvulsive effect through the CB1 receptor, while intracellular anandamide accumulation is proconvulsive through TRPV1.

Keywords

2-Arachidonoylglycerol ABHD6 Anandamide CB1 receptor MAGL Rat TRPV1 

Notes

Acknowledgments

The authors wish to thank Dr. M. Elahdadi Salmani for significant English language editing. The authors would like to thank Dr. Liang Zhang for his valuable comments. This study was supported by Arak University of Medical Sciences (funding numbers: 2390 & 2394).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interests.

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Authors and Affiliations

  1. 1.Department of Physiology, Faculty of MedicineArak University of Medical SciencesArakIran
  2. 2.Division of Fundamental NeurobiologyKrembil Research InstituteTorontoCanada

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