Serotonin3 antagonists block aversion to saccharin in an amino acid-imbalanced diet

Conditioned taste aversion presumably plays a role in the anorectic responses to amino acid-imbalanced diets that induce acute amino acid deficiency. The serotonin3 (5-HT3) receptor antagonists, tropisetron (Trop), MDL-72222 (MDL), and ondansetron, increase intake of imbalanced amino acid diets. Therefore, we tested whether 5-HT3 receptor antagonists would block an aversion to powdered saccharin after it was included in an amino acid-imbalanced diet. Rats were given an intraperitoneal injection of Trop, MDL, or vehicle (Veh), just before introducing one of four diets: imbalanced amino acid diet +/- saccharin (Imb or ImbSac) or a balanced (corrected) diet +/- saccharin (Cor or CorSac). Subsequent aversion to saccharin was shown in preference tests using Cor and CorSac. Saccharin preference was significantly decreased (8.3% on test day 1) in the Veh/ImbSac group, but the Trop/ImbSac group's saccharin preference (57.8%) was similar to controls (49.6-70.3%); MDL also blocked the aversion to saccharin after ImbSac. This confirms previous reports of conditioned taste aversions with amino acid limitation and suggests a role for the 5-HT3 receptor in the development of these aversions.