Although inverse agonist properties are attributed to the cannabinoid-1 receptor (CB1R) antagonist SR141716A, no independent effect has been observed for this ligand in the bioassay of cannabinoid inhibition of the KCl-evoked increase in free intacellular calcium concentration ([Ca2+]i) measured by microfluorimetry in either rat (Khasabova et. al., 2002) or mouse (Khasabova et al., 2005, SFN abstract) dissociated dorsal root ganglion (DRG) neurons in vitro. In this model, SR141716A effectively blocks the inhibitory effect of synthetic CB1R agonists on medium-large size DRG neurons. In recent studies of endocannabinoids on DRG neurons, anandamide (AEA) alone had no effect on this population of DRG neurons, but SR141716A+AEA resulted in inhibition of the KCl-evoked increase in [Ca2+]i. Responses to another CB1R antagonist, AM251, in the absence and presence of AEA paralleled responses to SR141716A suggesting that the ability of CB1R antagonists to uncover an effect of AEA is not specific to one drug but rath...