in rats: To benchmark imaging data against potential CNS side effects of A-834735 using traditional in vivo behaviour assays, rotarod performance and spontaneous exploratory behaviour were assessed in naive rats. Each rat was given three training sessions and then rotorod performance (mean latency to fall from the rotorod) was determined 30 min following i.p. administration of vehicle or A-834735 (0.5, 1.5 or 5 μmol kg−1). For spontaneous exploratory behaviour, a total of 40 rats (n=8 per group) were injected i.p. with vehicle (5% dimethyl sulphoxide/PEG400) or A-834735 (0.5, 1.5, 5 and 15 μmol kg−1) in a volume of 2 ml kg−1 and returned to their home cages.

Doses of A-834735 that produce CB1-mediated changes in brain activity detected by phMRI produce sufficient brain concentrations to bind CB1 and CB2 receptors and induce a functional effect, as predicted by in vitro Ki and EC50 data in binding and cAMP assays. A-834735 acts as a full agonist at both the central CB1 and peripheral CB2 receptors in rat with Ki values of 4.6 and 0.31 nM, respectively and EC50 values of 12 and 0.21 nM, respectively.