Vanilloid VR1 receptor is involved in rimonabant-induced neuroprotection.
Recently, a potential neuroprotective effect of rimonabant, independent of the CB1 receptor interaction, has been proposed. In the present study, the role of transient receptor potential channel vanilloid subfamily member 1, named VR1, 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 CA1 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 VR1 vanilloid receptor antagonist, completely reversed rimonabant-induced neuroprotective effects against EEG flattening, memory impairment and CA1 hippocampal neuronal loss. These findings suggest that VR1 vanilloid receptors are involved in rimonabant's neuroprotection even if other mechanisms can contribute to this effect.
Pegorini
Simona
S
Department of Pharmacology, Chemotherapy and Medical Toxicology, Faculty of Sciences, University of Milan, Via Vanvitelli 32, Milan 20129, Italy.
Zani
Alessia
A
Braida
Daniela
D
Guerini-Rocco
Chiara
C
Sala
Mariaelvina
M
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy; D063387:Cannabinoid Receptor Antagonists; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects; D005849:Gerbillinae; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D000077285:Rimonabant; D050916:TRPV Cation Channels / Q000187:drug effects / Q000502:physiology*
D063387:Cannabinoid Receptor Antagonists; D018696:Neuroprotective Agents; D010880:Piperidines; D011720:Pyrazoles; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C071423:capsazepine; D000077285:Rimonabant; D002211:Capsaicin