Vanilloid VR 1 receptor is involved in rimonabant-induced neuroprotection

Simona Pegorini, Alessia Zani, Daniela Braida, Chiara Guerini-Rocco, Mariaelvina Sala

Research output: Contribution to journalArticle

Abstract

Recently, a potential neuroprotective effect of rimonabant, independent of the CB 1 receptor interaction, has been proposed. In the present study, the role of transient receptor potential channel vanilloid subfamily member 1, named VR 1, on neuroprotective effect of rimonabant, on global cerebral ischemia in gerbils, was investigated. Rimonabant (0.05-3 mg kg -1), given i.p. 5 min after recirculation, dose dependently antagonized the ischemia-induced decrease in electroencephalographic (EEG) total spectral power and restored relative frequency band distribution 7 days after ischemia. Rimonabant (0.125-0.5 mg kg -1) fully prevented ischemia-induced hyperlocomotion 1 day after ischemia and memory impairment evaluated in a passive avoidance task, 3 days after ischemia. At 7 days after ischemia, the survival of pyramidal cells, in the CA 1 subfield, was respectively 91 and 96%, in the animals given rimonabant 0.25 and 0.5 mg kg -1, compared to the vehicle group. Higher doses were not protective. The protection induced by rimonabant followed a bell-shaped curve, the maximal active doses being 0.25 and 0.5 mg kg -1. Capsazepine (0.01 mg kg -1), a selective VR 1 vanilloid receptor antagonist, completely reversed rimonabant-induced neuroprotective effects against EEG flattening, memory impairment and CA 1 hippocampal neuronal loss. These findings suggest that VR 1 vanilloid receptors are involved in rimonabant's neuroprotection even if other mechanisms can contribute to this effect.

Original languageEnglish
Pages (from-to)552-559
Number of pages8
JournalBritish Journal of Pharmacology
Volume147
Issue number5
DOIs
Publication statusPublished - Mar 2006

Keywords

  • Cannabinoid antagonist
  • EEG
  • Global cerebral ischemia
  • Memory
  • Motor activity gerbil
  • SR 141716
  • Vanilloid receptor

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'Vanilloid VR 1 receptor is involved in rimonabant-induced neuroprotection'. Together they form a unique fingerprint.

  • Cite this

    Pegorini, S., Zani, A., Braida, D., Guerini-Rocco, C., & Sala, M. (2006). Vanilloid VR 1 receptor is involved in rimonabant-induced neuroprotection. British Journal of Pharmacology, 147(5), 552-559. https://doi.org/10.1038/sj.bjp.0706656