Serotonin Receptor Blockade Increases Food Intake and Body Weight after Total Gastrectomy in Rats

Abstract

Background. Total gastrectomy often results in early satiety and loss of body weight. Serotonin inhibits food intake, and postprandial serotonin release is increased after total gastrectomy. Serotonin might contribute to early satiety and loss of body weight after total gastrectomy. Methods and materials. Food intake and body weight were investigated with an automated recording system in gastrectomized rats 1–12 months postoperatively. Rats were treated with metergoline, a 5-hydroxytryptamine (5-HT) 1/2 receptor antagonist, two different 5-HT 3 receptor antagonists, a combination of metergoline and devazepide, a cholecystokinin (CCK) a receptor antagonist, or vehicle. In addition, metergoline or vehicle was applied continuously by an intraperitoneal osmotic minipump for 7, 28, or 84 days after total gastrectomy. Results. Metergoline treatment resulted in a dose-dependent increase in food intake in gastrectomized rats. 5-HT 3 receptor antagonist treatment had no effect, and devazepide in addition to metergoline did not further stimulate food intake. Metergoline increased food intake at 1, 3, and 6 months postoperatively by up to 45% (24-h cumulative food intake [FI], 6 months: vehicle 3.83 ± 0.10, metergoline 5.52 ± 0.15 g/100 g body weight (BW), P < 0.0001). Chronic metergoline treatment for 7, 28, or 84 days significantly increased food intake after total gastrectomy compared to vehicle treatment (FI 7 days: vehicle 30.83 ± 0.71, metergoline 36.27 ± 0.85 g/100 g BW; P < 0.0002; average weekly FI during 28 days; vehicle 31.23 ± 0.22, metergoline 36.83 ± 0.33 g/100 g BW, P < 0.0001; average weekly FI during 84 days: vehicle 33.02 ± 0.59, metergoline 35.07 ± 0.48 g/100g BW, P < 0.008), and there was a significant body weight increase compared to vehicle treatment (7 days: ΔBW vehicle −0.7 ± 1.2 g vs ΔBW metergoline 9.0 ± 2.1 g, P < 0.001; 28 days: ΔBW vehicle 0.3 ± 2.2 vs ΔBW metergoline 13.0 ± 2.3, P < 0.001; 84 days: ΔBW vehicle 25.7 ± 10.2 vs ΔBW metergoline 49.5 ± 7.2, P < 0.04). Treatment for 84 days resulted in a significant body weight gain, while vehicle treatment had no effect (vehicle: 438 ± 11 g vs 464 ± 12 g, P < 0.2, n.s.; metergoline: 448 ± 9 g vs 498 ± 10 g, P < 0.007). Conclusions. Inhibition of food intake by serotonin might contribute to early satiety and loss of body weight after total gastrectomy.