Figure 3 shows the results of tests with THC, URB597, and a combination of URB597/JZL184 in rats trained to discriminate 3 mg/kg THC from vehicle. THC produced dose-dependent substitution, with an ED50 value of 1.3 mg/kg (95% CI: 0.76 – 2.10 mg/kg) [Fig. 3, panel A]. In contrast, URB597 failed to produce significant substitution for THC at any dose tested (Fig. 3, panel A). URB597 (30 mg/kg) was then tested in combination with 16 mg/kg JZL184, a dose that did not substitute by itself. The results of this probe test showed that the combination of 30 mg/kg URB597 and 16 mg/kg JZL184 (Fig. 3, right side of panel A) significantly increased responding on the THC-associated lever compared to average responding following URB597 and JZL184 vehicles (at left and right sides of Fig. 3, panel A) [F(2,8)=4.93, P<0.05], without alteration of overall response rate. Whereas response rates following administration of 10 mg/kg THC were significantly decreased compared to rates obtained after vehicle injection [F(4,28)=13.44, P<0.05], URB597 did not affect response rates compared to vehicle (Fig. 3, panel C).
