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 central relay in a neural network which controls food intake. The non-competitive NMDA antagonist MK-801 facilitates food intake in rats by acting on the NTS. Here we report that hepatic portal vein infusion of MK-801 (25 or 50 microg/kg) increases intake of an intraorally infused 1 M solution of sucrose (by 113 +/- 9 and 132 +/- 11%, respectively) and that this effect is prevented by hepatic vagotomy. By contrast, jugular vein infusion of MK-801 fails to increase sucrose intake but induces forward locomotion, indicating activation of a central mechanism. These data suggest that MK-801 can stimulate food intake by acting peripherally on hepatic vagal afferents.