Fig. 3. Effects of the adenosine A2A antagonist preladenant (PL) on effort-related choice behavior. (A and B) Ability of the adenosine A2A antagonist preladenant to reverse the effects of tetrabenazine (TBZ) in rats responding on the concurrent FR5/chow choice task. All rats (n = 13; adult male, Sprague–Dawley rats; Harlan Sprague–Dawley, Indianapolis, IN) were trained on the FR5/chow-feeding choice procedure, as described in Yohn et al. (2016b,d,e), and tested in 30-minute sessions. Rats were tested 5 days per week, and, after several weeks of training, drug testing was conducted 1 day each week, with a randomized order of drug treatments. All animals received intraperitoneal (IP) injections of vehicle or 0.75 mg/kg tetrabenazine 120 minutes prior to testing, and also received IP injections of vehicle or preladenant IP (0.05, 0.1, 0.2 mg/kg) 25 minutes prior to testing. (A) Lever pressing. Mean (± S.E.M.) number of lever presses in the 30-minute session are shown. There was an overall significant effect of drug treatment on lever pressing [F(4,48) = 12.0, P < 0.001]. Planned comparisons showed that TBZ significantly decreased lever pressing compared with vehicle (#P < 0.05), and that all doses of preladenant plus TBZ significantly increased lever pressing relative to TBZ plus vehicle (*P < 0.01). (B) Chow intake. Mean (± S.E.M.) gram quantities of chow intake are shown. There was an overall significant effect of drug treatment on chow intake [F(4,48) = 7.43, P < 0.001]. Planned comparisons showed that TBZ significantly increased chow consumption relative to vehicle (#P < 0.05), and that all doses of preladenant plus TBZ significantly decreased chow intake relative to TBZ plus vehicle (*P < 0.01). (C and D). Effect of preladenant in rats responding on the PROG/chow-feeding choice task. The rats that were used for the FR5/chow-feeding experiment (n = 13) were then trained on the concurrent PROG/chow-feeding choice task, as described by Yohn et al. (2016a). Rats were tested 5 days per week, and, after several weeks of training, drug testing was conducted 1 day each week, with a randomized order of drug treatments. All animals received IP injections of vehicle or preladenant IP (0.1, 0.2, 0.4 mg/kg) 25 minutes prior to testing. (C) Lever pressing. Mean ± S.E.M. number of lever presses in the 30-minute session is shown. There was an overall significant effect of drug treatment on PROG lever pressing [F(3,36) = 3.7, P < 0.05]. Planned comparisons showed that the highest dose of preladenant (0.4 mg/kg) significantly increased lever pressing relative to vehicle (*P < 0.05). (D) Chow intake. Mean (± S.E.M.) gram quantities of chow intake are shown. The overall tendency of preladenant administration to decrease chow intake approached statistical significance [F(3,36) = 2.63, P = 0.065]. [All results from this figure were presented at the 2017 Society for Neuroscience meeting (Rotolo et al., 2017).]