Subchronic D-Fenfluramine Treatment Enhances the Immunological Competance of Old Female Fischer 344 Rats

Young (5 mo) and old (21 mo) female Fischer 344 (F344) rats received the serotonin (5-HT) releaser and reuptake inhibitor, d-fenfluramine (d-Fen; 0.6 mg/kg/day, p.o.), in their deionized drinking water for 30–38 days. The control animals had access ad libitum to deionized water. In comparison to the young animals, the old rats showed a significantly higher percentage of splenic large granular lymphocytes (%LGL) and greater concanavalin A (Con-A) stimulated T cell proliferation. The old d-Fen treated rats, furthermore, showed a significant: 1) further increase in %LGL; 2) enhancement of both basal and recombinant interleukin-2 (rIL-2) stimulated natural killer cytotoxicity; and, 3) augmentation of lipopolysaccharide (LPS) induced B cell mitogenesis. d-Fenfluramine did not affect any of the immunological parameters studied in the yound rats, and did not affect the animals’ body weights, 24 h fluid intakes, or the levels of medial frontal cortex monoamines and their metabolites. These data suggest that prolonged 5-HT release and/or reuptake inhibition enhances immune competence in old but not in young female F344 rats.