Hypolocomotor effects in rats of capsaicin and two long chain capsaicin homologues

Capsaicin and its analogue N-arachidonoyl-vanillyl-amine (arvanil) are agon ists of vanilloid VR, receptors. and suppress spontaneous activity in mice through an unknown mechanism. Here, we tested in rats the effect on motor b ehavior of: (1) capsaicin; (2) N-linoleoyl-vanillyl-amine (livanil) and N-a lpha -linolenoyl-vanillyl-amine (linvanil), which, unlike arvanil, have ver y little affinity for cannabinoid CB1 receptors; and (3) the endocannabinoi d anandamide ( N-arachidonoyl-ethanolamine), which is a full agonist at bot h cannabinoid CB1 and vanilloid VR, receptors. All compounds, administered i.p., dose-dependently (0.1-10 mg/kg) inhibited ambulation and stereotypic behavior and increased inactivity in the open field test. The rank of poten cy observed in vivo (livanil > capsaicin > linvanil > anandamide) bore litt le resemblance with the relative potencies in a functional assay for rat va nilloid VR1 receptors (livanil = linvanil > capsaicin > anandamide) and eve n less with the relative affinities in rat CB, receptor binding assays (ana ndamide > livanil > linvanil > capsaicin). The vanilloid VR1 receptor antag onist capsazepine (10 mg/kg, i.p.) blocked the effect of capsaicin but not of livanil or anandamide, whereas the CB1 receptor antagonist (N-(piperidin -1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1 H-pyrazole-3-ca rboxamide. HCl (SR141716A, 3 mg/kg, i.p.) antagonized the actions of the CB 1 receptor agonist Delta (9)-tetrahydrocannabinol, but not of livanil, anan damide or capsaicin. Anandamide occluded the effects of livanil on locomoti on, possibly suggestive of a common mechanism of action for the two compoun ds. Finally, stimulation with capsaicin of cells expressing rat vanilloid V R1 receptors led to anandamide formation. These data suggest that motor beh avior can be suppressed by the activation of: (1) vanilloid receptors, poss ibly via the intermediacy of anandamide; or (2) capsazepine- and SR141716A- insensitive sites of action for anandamide, livanil and linvanil, possibly the same that were previously suggested to mediate arvanil hypokinetic effe cts in mice. (C) 2001 Elsevier Science B.V. All rights reserved.