Article Figures & Data
Figures
- Figure 1.
GLP-1 receptor stimulation with EX4 decreased food-reward behavior. The effects of intraperitoneal injection of EX4 on PR operant responding for sucrose and the ability of chocolate to condition a place preference were tested. A, EX4 decreased number of sucrose rewards earned in an operant lever-pressing paradigm. ***p < 0.0005, compared with vehicle using Tukey test; n = 16–48 per group. B, Preference for the chamber paired to palatable food was attenuated by EX4 treatment. The increased preference (% CPP) was calculated using the following formula: [(test − pre-test)/(total time − pre-test)] × 100. *p < 0.05, comparing vehicle to EX4 using Student's t test. C, Exploratory activity was not altered by the EX4 treatment during the CPP test; n = 9 per treatment group. Data represent mean ± SEM.
- Figure 2.
Central (ICV) administration of EX4 is sufficient to decrease food-motivated behavior in PR operant responding for a sucrose reward paradigm. *p < 0.05, **p < 0.005, ***p < 0.0005 comparing vehicle to each EX4 dose using the Tukey test after obtaining a significant main effect by one-way ANOVA for each time point; n = 2–10. Data represent mean ± SEM.
- Figure 3.
Central EX4 reduction in food-reward behavior is mediated via GLP-1Rs as pretreatment with a selective GLP-1R antagonist, EX3, abolishes the suppressive effect of EX4 on PR operant conditioning. ***p < 0.0005 comparing vehicle to EX4 using the Tukey test after detecting a significant interaction of pretreatment with EX4 in two-way ANOVA and a main effect of one-way ANOVA; n = 8. Data represent mean ± SEM.
- Figure 4.
VTA GLP-1R stimulation is sufficient to suppress food intake and reward behavior. The effects of microinjection of EX4 into the VTA on chow intake and PR operant conditioning for sucrose were tested. A, Graphical representation (left) and representative tissue section (right) showing VTA microinjection site determined with India ink, used in the study. Aq, aquaduct; cp, cerebralpeduncle; SN, substantia nigra; ml, medial lemniscus. B, VTA microinjection of EX4 produced chow anorexia. **p < 0.05, comparing vehicle to EX4 using a Tukey test after detecting a significant main effect by one-way ANOVA; n = 16. C, The number of sucrose pellets earned in the PR operant test was significantly decreased by EX4 VTA microinjection. *p < 0.05, **p < 0.005, ***p < 0.0005 comparing vehicle to each EX4 dose using the Tukey test after detecting a significant main effect of one-way ANOVA for each time point; n = 15. Data represent mean ± SEM. D, E, The number of changes in horizontal and vertical (rearing) spontaneous motor activity was measured after VTA directed EX4 injection; n = 11.
- Figure 5.
NAc GLP-1Rs contribute to food intake and reward behavior regulation. The effects of microinjection of EX4 into the NAc on chow intake and PR operant conditioning for sucrose were tested. A, Graphical representation (left) and representative tissue section (right) showing the NAc microinjection site determined with India ink, used in the study. CPu, caudate and putamen; NAccC, nucleus accumbens core, NAccS, nucleus accumbens shell. B, NAc microinjection of EX4 produced chow anorexia. **p < 0.005, comparing vehicle to each EX4 dose using the Tukey test after detecting a significant main effect by one-way ANOVA; n = 15. C, The number of sucrose pellets earned in the PR operant test was significantly decreased by EX4 NAc microinjection. *p < 0.05, **p < 0.005 comparing vehicle to each EX4 dose using the Tukey test after detecting a significant main effect of one-way ANOVA for each time point; n = 16. Data represent mean ± SEM. D, E, The number of changes in horizontal and vertical (rearing) spontaneous motor activity was decreased only 10–20 min after NAc EX4 injection and unaltered for the remaining 50 min of measurement. *p < 0.05, **p < 0.005 comparing vehicle to EX4 using Student's t test; n = 16.
- Figure 6.
VTA and NAc GLP-1R activation effects on 24 h chow intake and body weight. VTA GLP-1R activation potently reduced chow intake (A) and body weight gain (B). In contrast, NAc shell GLP-1 activation produced a small reduction in 24 h chow intake (C) and did note alter body weight gain (D). ***p < 0.0005 comparing vehicle to each EX4 dose using the Tukey test after detecting a significant main effect of one-way ANOVA for each time point; n = 15. Data represent mean ± SEM.
- Figure 7.
VTA GLP-1R stimulation in overnight ad libitum-fed rats is sufficient to suppress food intake and reward behavior. The effects of microinjection of EX4 into the VTA on chow intake and PR operant conditioning for sucrose in satiated rats were tested. A, The number of sucrose pellets earned in the PR operant test was significantly decreased by EX4 VTA microinjection. B, Number of rewards earned by the satiated animals analyzed by dividing them into those with a high motivation to work for sucrose at their satiated baseline (on the vehicle condition earned 6 or more rewards; n = 6) and those displaying a low motivation for sucrose (on vehicle earned 5 or less rewards; n = 8). These data might indicate an enhanced sensitivity to the reward reducing effects of EX4 in high reward responders, i.e., those rats are highly motivated to earn sucrose despite their satiated state. C, D, VTA microinjection of EX4 reduced free-feeding on chow at both the 1 h and the 24 h time points. *p < 0.05, **p < 0.005 comparing vehicle to each EX4 dose using the Tukey test after detecting a significant main effect of one-way ANOVA for each time point; n = 14. Data represent mean ± SEM.
- Figure 8.
EX4 VTA (A) and NAc (B)-directed microinjection-induced anorexia is not accompanied by a malaise response, as EX4 dose effective in producing a reduction in chow intake did not simultaneously increase kaolin consumption. *p < 0.05, ***p < 0.0005 comparing vehicle to each EX4 dose using the Tukey test after detecting a significant main effect of one-way ANOVA for each time point; n = 4–8. Data represent mean ± SEM.
