** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** ANNUAL ECONOMIC LOSS FOR THE UNITED STATES BEEF INDUSTRY DUE TO TALL FESCUE TOXICOSIS WAS ESTIMATED TO BE $2 BILLION, OF WHICH $500 MILLION WAS DUE TO DECREASED GROWTH OF CALVES CONSUMING TALL FESCUE CONTAINING ERGOT ALKALOIDS. ERGOT ALKALOIDS DECREASE FEED INTAKE, INCREASEVASOCONSTRICTION OF CORE AND PERIPHERAL BLOOD VESSELS, AND POSSIBLY CONTRIBUTE TO IMMUNE SYSTEM ACTIVATION. THE OVERALL GOAL OF THIS PROJECT IS TO EVALUATE THE POTENTIAL FOR 5-HYDROXYTRYPTOPHAN (5-HTP) TO AMELIORATE FESCUE TOXICOSISIN BEEF CATTLE. THE OBJECTIVES OF THIS PROJECT ARE TO DETERMINE: 1) IF INCREASING SERUM SEROTONIN (5-HT) WITH 5-HTP RESTORES FEED INTAKE, 2) IF INCREASING SERUM 5-HT WITH 5-HTP CAUSES VASODILATION OF ERGOT ALKALOID-CONSTRICTED BLOOD VESSELS AND REDUCES SUSCEPTIBILITY TO HEAT STRESS, 3) IF ALLEVIATING ERGOT ALKALOID-INDUCED VASOCONSTRICTION AND HEAT STRESS ARE ASSOCIATED WITH REPAIRING COMPROMISED IMMUNE SYSTEM FUNCTION AND GUT INTEGRITY, AND 4) IDENTIFYING GENES AND PATHWAYS ASSOCIATED WITH THE ONSET AND AMELIORATION OF FESCUE TOXICOSIS BY ERGOT ALKALOIDS AND 5-HTP, RESPECTIVELY.IT IS ANTICIPATED THAT THIS PROJECT WILL LEAD TO THE FIRST REPORT DEMONSTRATING THAT: INCREASED SERUM 5-HT FROM 5-HTP WILL LEAD TO INCREASED VASORELAXATION, RESTORED DRY MATTER INTAKE, AND DECREASED IMMUNOACTIVATION ANDRNA-SEQ ANALYSIS OF BLOOD VESSELS, HYPOTHALAMUS, AND INTESTINAL TISSUE WILL IDENTIFY GENES, PATHWAYS, AND FUNCTIONS ASSOCIATED WITH THESE PHENOTYPIC RESPONSES. THIS NEW KNOWLEDGE WILL AID IN EFFORTS TO DEVELOP STRATEGIES TO AMELIORATE FESCUE TOXICOSIS IN GRAZINGBEEF CATTLE.