Evidence that MK-801 stimulates intraoral intake by acting on hepatic afferents

Satiety signals from the gastrointestinal tract travel via vagal afferents to the nucleus of the solitary tract (NTS) in the brain stem, the first cen tral relay in a neural network which controls food intake. The non-competit ive NMDA antagonist MK-801 faciliates food intake in rats by acting on the NTS. Here we report that hepatic portal vein infusion of MK-801 (25 or 50 m u g/kg) increases intake of an intraorally infused IM solution of sucrose ( by 113+/-9 and 132+/-11%, respectively) and that this effect is prevented b y hepatic vagotomy. By contrast, jugular vein infusion of MK-801 fails to i ncrease sucrose intake but induces forward locomotion, indicating activatio n of a central mechanism. These data suggest that MK-801 can stimulate food intake by acting peripherally on hepatic vagal afferents. (C) 2000 Lippinc ott Williams & Wilkins.