The role of medial hypothalamic serotonin in the suppression of feeding ina rat model of colitis

Background & Aims: Experimental colitis is associated with anorexia that is attenuated by treatment with an interleukin (IL)-1 receptor antagonist. Se rotonin (5-hydroxytryptamine [5-HT]) is a potent inhibitor of feeding, and its release from the hypothalamus is stimulated by IL-1. We have tested the hypotheses that anorexia associated with experimental colitis results from increased activity of hypothalamic 5-HT neurons and that the increase in a ctivity occurs secondary to an increase in availability of tryptophan, the precursor of 5-HT. Methods:ln vivo 5-HT release and regional hypothalamic 5 -HT and tryptophan concentrations were measured in rats with 2,4,6,-trinitr obenzene sulfonic acid (TNBS)-induced colitis, healthy controls, and animal s pair-fed to match the food intake of the colitic group. Food intake in th e colitic group was assessed after depletion of brain 5-HT by p-chloropheny lalanine (PCPA). Results: In the colitic group, release of 5-HT from the hy pothalamic paraventricular nucleus (PVN) was 3-fold (P = 0.01) and 14-fold (P < 0.001) higher than in control and pair-fed groups, respectively. Conce ntrations of tryptophan were similar in each group in all hypothalamic regi ons. Food intake was significantly increased in the colitic group after PCP A treatment but was not restored to control values, Conclusions: In animals with TNBS-induced colitis, 5-HT release from the PVN is increased, The inc rease in food intake after depletion of brain 5-HT suggests that hypothalam ic 5-HT contributes to anorexia but is not the only mediator, Increased 5-H T release in the colitic group was not driven by increased precursor availa bility.