Abstract
tration of m-CPP and fenfluramine to fasted rats altered the fasted motor activities in the antrum and duodenum to fed-like motor activities and the phase III-like contractions were significantly decreased. Treatment with the 5-HT2cR antagonist (SB242084), but not the 5-HT1bR (SB224289) and 5-HT2bR (SB215505) antagonists, was able to restore the fasted motor patterns in the antrum and duodenum of fenfluramine-treated rats. SB242084 also inhibited the decrease in plasma acyl ghrelin induced by fenfluramine. The MC4R (HS014) and MC3/4R (SHU9119) antagonists failed to modify the decreased motor activities induced by fenfluramine. In contrast, ghrelin and NPY restored the fasted motor patterns in the antrum and duodenum of fenfluramine-treated rats. Administration of phentolamine and hesperidine, which stimulate the secretion of endogenous acyl ghrelin, successfully restored the fasted motor activities in fenfluramine-treated rats. CONCLUSION: The present study has elucidated a novel central 5-HT2c receptor pathway regulating physiological GI motor activity. These results demonstrate direct neuroendocrine control over GI function by central 5-HT2c receptors, which inhibit ghrelin-NPY signaling.
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