Furthermore, treatment with exendin-4 or LiCl attenuated the percent of saccharine intake compared to treatment with liraglutide (both values 0

Furthermore, treatment with exendin-4 or LiCl attenuated the percent of saccharine intake compared to treatment with liraglutide (both values 0.001). with partial rehydration (WD-PR). Each agonist suppressed AngII-induced water intake; however, only exendin-4 suppressed saline intake. WD-PR-induced water and saline intakes were both attenuated by each agonist. Analysis of drinking microstructure after WD-PR found a reliable effect of the agonists on burst number. Furthermore, exendin-4 conditioned a strong taste avoidance to saccharine; however, there was no similar effect of liraglutide. To evaluate the relevance of the conditioned taste avoidance, we tested whether inducing visceral malaise by injection of lithium chloride (LiCl) suppressed fluid intake. Injection of LiCl did not suppress water or saline intakes. Overall, these results indicate that this fluid intake suppression by GLP-1R activation is not selective to water intake, is usually a function of post-ingestive opinions, and is not secondary to visceral malaise. access to water and 1.5% saline for at least 5 d prior to testing. Approximately 2 h after lights on, food and fluids were removed and rats received a pretreatment injection of liraglutide (0.05 g), exendin-4 (0.05 g), Cdh15 or vehicle (1 l 0.9% saline) into the LV. These drugs have been shown to have a delayed effect on dark phase water intake (21), therefore, 2 hr after the pretreatment, a test injection of AngII (100 ng) was administered into the LV. Water and saline bottles then were made available, and fluid intake was measured for the subsequent two hours. Food was returned after the two-hour Nandrolone fluid intake test. This experiment was conducted with a repeated steps design. Rats received each treatment condition in a partial Latin squares design and screening days were separated by 3C5 d. Total water intake data from two animals were removed from analysis due to bottle leakage. Experiment 2: Effect of GLP-1R agonists on altered WD-PR-induced water and saline intakes Rats were habituated to two-bottle access to both water and 1.5% saline for at least 5 d prior to testing. The traditional WD-PR process (25) was altered as explained below for this experiment to account for the longer acting effects of liraglutide and exendin-4 (21). Using a between subjects design, rats experienced fluids removed 24 hr prior to an injection of liraglutide (0.05 g; n=5), exendin-4 (0.05 g; n=5), or vehicle (1 l 0.9% saline; n=5). Immediately after the injection, rats were given access to 7 ml of water (partial rehydration period). Because our pilot studies found that GLP-1R agonists suppressed water intake during the rehydration period, we altered the WD-PR process so that each rat was only allowed to drink 7 ml of water. This volume was consumed by all rats, regardless of treatment condition. After the partial rehydration period, water and saline, but not food, were returned and fluid intake was measured for two hours. Total water intake data from one animal treated with exendin-4 was removed from analysis due to bottle leakage. Lick patterns also were analysed as explained in below. Experiment 3: Does exendin-4 (0.05 g) or liraglutide (0.05 g) condition a taste avoidance? Rats were habituated to a restricted drinking routine during which they had access to Nandrolone two bottles of water for 90 min each day, beginning approximately 2 h after lights on. After 7 d on this routine, rats were given access to two bottles of 0.1% saccharine, instead of water, for 90 min. Immediately after saccharine exposure, rats were given an LV injection of liraglutide (0.05 g; n=7), exendin-4 (0.05 g; n=6), or vehicle (0.9% saline; n=4), or an ip injection of lithium chloride Nandrolone (LiCl; 0.15 M, 1.33 ml/100 g body weight; n=5). Forty eight hours later, rats were given a two-bottle test for saccharine preference during the normally scheduled water intake. To ensure that a.