Studies on the role of 5-HT receptors in satiation and the effect of d-fenfluramine in the runway test.

d-Fenfluranine has previously been shown to reduce food-rewarded runway behaviour in the rat, an effect thought to be mediated through activation of central 5-HT pathways. We now examined in more detail the mechanism by which d-fenfluramine reduces runway performance and food intake in the 15-trial runway test. The non-selective 5-HT receptor antagonist, metergoline (1.0 mg/kg), significantly antagonised the effect of d-fenfluramine (2.5 mg/kg) in the runway test. In contrast, neither ritanserin, the potent 5-HT2 and 5-HT1C receptor antagonist (0.5 mg/kg), nor the peripheral 5-HT receptor antagonist, xylamidine (3.0 mg/kg), attenuated the effect of d-fenfluramine in this test situation. Metergoline, but not ritanserin or xylamidine significantly increased runway performance when administered alone. These data indicate that d-fenfluramine reduces runway performance and food intake through activation of 5-HT1 receptors. In addition, blockade of 5-HT1 receptors can attenuate the development of satiation normally observed under control conditions in the runway test.