Capsaicin exhibits neuroprotective effects in a model of transient global cerebral ischemia in Mongolian gerbils

1 Capsaicin, the irritant principle of hot peppers, is a vanilloid agonist known to activate the transient receptor potential channel vanilloid subfamily member 1 (VR1), recently reported to be involved in neurodegeneration. The present study investigated the role of VR1 in a model of global cerebral ischemia in gerbils. 2 Over the dose range tested, capsaicin (0.01, 0.025, 0.05, 0.2 and 0.6 mg kg −1 ), given 5 min after recirculation, dose‐dependently antagonized the ischemia‐induced electroencephalographic total spectral power decrease and restored relative frequency band distribution evaluated 7 days after ischemia. 3 Capsaicin, at all tested doses, fully prevented ischemia‐induced hyperlocomotion evaluated 1 day after ischemia. 4 Capsaicin dose‐dependently antagonized ischemia‐induced memory impairment evaluated in a passive avoidance task, 3 days after ischemia. 5 Capsaicin showed a dose‐dependent hypothermic effect evaluated for 2 h after recirculation. 6 At 7 days after ischemia, a progressive survival of pyramidal cells in the CA1 subfield in capsaicin‐treated gerbils, with a maximum of 80%, at a dose of 0.2 mg kg −1 , was obtained. 7 The selective VR1 antagonist, capsazepine (0.01 mg kg −1 ), reversed capsaicin‐induced protective effects, in a competitive manner. 8 These results suggest that the neuroprotective effect of capsaicin may be attributable, at least in part, to VR1 desensitization and provide a valuable target for development of interventional pharmacological strategies.British Journal of Pharmacology (2005) 144 , 727–735. doi: 10.1038/sj.bjp.0706115