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

67 Citations (Scopus)

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

Fingerprint

rimonabant
Ischemia
Neuroprotective Agents
Transient Receptor Potential Channels
vanilloid receptor subtype 1
Neuroprotection
Gerbillinae
Pyramidal Cells
Brain Ischemia

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

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

Vanilloid VR 1 receptor is involved in rimonabant-induced neuroprotection. / Pegorini, Simona; Zani, Alessia; Braida, Daniela; Guerini-Rocco, Chiara; Sala, Mariaelvina.

In: British Journal of Pharmacology, Vol. 147, No. 5, 03.2006, p. 552-559.

Research output: Contribution to journalArticle

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, vol. 147, no. 5, pp. 552-559. https://doi.org/10.1038/sj.bjp.0706656
Pegorini, Simona ; Zani, Alessia ; Braida, Daniela ; Guerini-Rocco, Chiara ; Sala, Mariaelvina. / Vanilloid VR 1 receptor is involved in rimonabant-induced neuroprotection. In: British Journal of Pharmacology. 2006 ; Vol. 147, No. 5. pp. 552-559.
@article{71965856ab134fed9b62dd81b53905a0,
title = "Vanilloid VR 1 receptor is involved in rimonabant-induced neuroprotection",
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.",
keywords = "Cannabinoid antagonist, EEG, Global cerebral ischemia, Memory, Motor activity gerbil, SR 141716, Vanilloid receptor",
author = "Simona Pegorini and Alessia Zani and Daniela Braida and Chiara Guerini-Rocco and Mariaelvina Sala",
year = "2006",
month = "3",
doi = "10.1038/sj.bjp.0706656",
language = "English",
volume = "147",
pages = "552--559",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Vanilloid VR 1 receptor is involved in rimonabant-induced neuroprotection

AU - Pegorini, Simona

AU - Zani, Alessia

AU - Braida, Daniela

AU - Guerini-Rocco, Chiara

AU - Sala, Mariaelvina

PY - 2006/3

Y1 - 2006/3

N2 - 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.

AB - 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.

KW - Cannabinoid antagonist

KW - EEG

KW - Global cerebral ischemia

KW - Memory

KW - Motor activity gerbil

KW - SR 141716

KW - Vanilloid receptor

UR - http://www.scopus.com/inward/record.url?scp=33644830973&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644830973&partnerID=8YFLogxK

U2 - 10.1038/sj.bjp.0706656

DO - 10.1038/sj.bjp.0706656

M3 - Article

C2 - 16444289

AN - SCOPUS:33644830973

VL - 147

SP - 552

EP - 559

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 5

ER -