Finally, MJN110 did not alter consumption of freely available sucrose within volumes obtained in the operant task. not alter consumption of freely available sucrose within volumes obtained in the operant task. Together these data demonstrate blocking endocannabinoid tone at the CB1 receptor attenuates the ability of cues to induce reward seeking, while some aspects of motivation for the reward are retained. Conversely, enhancing 2-AG signaling at CB1 receptors facilitates IC responding and increases the motivational properties of the IC. to the IC designating availability of sucrose (i.e. the ratio of active nosepokes resulting in a prize divided by the total number of ICs presented during a session). The is the time to emit a rewarded nosepoke after the start of the IC presentation (i ii, Physique 1a). The is the time to enter the receptacle after a rewarded nosepoke was emitted (iii iv, Physique 1a). The ratio of presented was also measured, and includes both rewarded and unrewarded nosepokes in the active port. The number of (i.e. those occurring during the ITI), the number of (i. e. those performed in the inactive port), and the number of were also decided. Latencies were measured only when a response was emitted and not when rats failed to respond to the IC. Data are presented as means the standard error of the mean (SEM). Statistical analyses were conducted by the software GraphPad Prism (version 8 for Windows). Statistical comparisons were conducted using one-way repeated steps (RM) ANOVAs (experiment 1 and 3) and two-way RM ANOVAs (experiment 2). All post-hoc pairwise IL15RA antibody comparisons were conducted using Holms-Sidak correction where the overall ANOVAs revealed statistical significance. Significance was set to = 0.05. Cumulative free drinking data were analyzed using two-way RM ANOVA, Holm-Sidak post-hoc pairwise comparisons, while total volume obtained was analyzed with paired-samples 0.0001), increased the latencies to respond to the cue (Figure 2b, one-way RM ANOVA, main effect of treatment: 0.0001) and enter the reward cup after a rewarded nosepoke (Physique 2c, one-way RM ANOVA, main effect of treatment: = 0.0011), and also reduced the number of active nosepokes per IC (Figure 2d, one-way RM ANOVA, main effect of treatment: 0.0001). One-way RM ANOVA yielded a main effect of treatment for the number of unrewarded nor-NOHA acetate active nosepokes per IC (Physique 2e, = 0.0224). However, post-hoc analysis did not reveal a significant dose effect. We did not observe an effect on the number of inactive nosepokes (Physique 2f) indicating that the rats distinguished between inactive and active ports. Cup entries per reward (Physique 2g) were also unchanged by rimonabant treatment, indicating that sucrose-seeking persisted even as the response ratio decreased. Open in a separate window Physique 2: Cannabinoid type 1 (CB1) receptor antagonism decreased responding to incentive cues, while some aspects of motivation for the sucrose reward were retained.Effects of the CB1 receptor antagonist rimonabant on (a) the response ratio, (b) the nosepoke latency, (c) the reward cup latency, (d) the number of active nosepokes per IC, (e) the number of unrewarded active nor-NOHA acetate nosepokes per IC, (f) the number of inactive nosepokes per IC, and (g) the number of cup entries per reward in nor-NOHA acetate the IC task in rats (n = 11). Data is usually expressed as mean SEM of an entire 1-h session. Statistically significant differences between drug dose and vehicle (V) as control treatment are indicated by asterisks (one-way repeated steps ANOVA, post-hoc Holm-Sidak correction, * 0.05, ** 0.01, *** 0.001, **** 0.0001). 3.2. MJN110 enhances responding in the decreasing reward IC task. In the altered version of the standard IC task used in experiment 2, the reward volume is decreased progressively every 15 min throughout the session from 64 l to 48 l, 32 l, and 16 l. This progression brings overall responding down and allowed us to investigate whether the MAGL inhibition increases responding to the IC in a second group of rats (n = 11). In the decreasing reward IC task, rats acquire lower baseline response ratios of ~60-70% for the entire 1-h session, compared to 80-90% baseline responding in the standard IC task. We first examined how different sucrose volumes alter responding in the decreasing reward IC task (Physique 3). Analysis of the vehicle data revealed an overall significant decrease in response ratio, increases in.