Roux-en-Y Gastric Bypass in Rats Increases Sucrose Taste-Related Motivated Behavior Independent of Pharmacological GLP-1-Receptor Modulation. Mathes CM

Roux-en-Y gastric bypass surgery (RYGB) has been shown to decrease consummatory responsiveness of rats to high sucrose concentrations, and genetic deletion of glucagon-like-1-peptide-receptors (GLP-1R) has been shown to decrease consummatory responsiveness of mice to low sucrose concentrations. Here we assessed the effects of RYGB and pharmacological GLP-1R modulation on sucrose licking by chow-fed rats in a brief access test that assessed consummatory and appetitive behaviors. Rats were tested while fasted presurgically and postsurgically, and while nondeprived postsurgically and 5h after intraperitoneal injections with the GLP-1R antagonist exendin-3(9-39) (30µg/kg), agonist exendin-4 (1µg/kg), and vehicle in 30-min sessions during which a sucrose concentration series (0.01-1.0M) was presented in 10-s trials. Other rats were tested postsurgically or 15min after peptide or vehicle injection while fasted and while nondeprived. Independent of food-deprivation state, sucrose experience, or GLP-1R modulation, RYGB rats took 1.5-3x as many trials as sham-operated rats, indicating increased appetitive behavior. Under nondeprived conditions, RYGB rats with presurgical sucrose experience licked more to sucrose relative to water compared with sham-operated rats. Exendin-4 and exendin-3(9-39) impacted 0.3M sucrose intake in a 1-bottle test, but never interacted with surgical group to affect brief access responding. Unlike prior reports in both clearly obese and relatively leaner rats given RYGB and GLP-1R knockout mice, we found that neither RYGB nor GLP-1R blockade decreased consummatory responsiveness to sucrose in our less obese chow-fed rats. Collectively, these results highlight the fact that changes in taste-driven motivated behavior to sucrose after RYGB and/or GLP-1R modulation are very model-and measure-dependent.