Effect of brain stem NMDA-receptor blockade by MK-801 on behavioral and Fos responses to vagal satiety signals

To test the possible role of N-methyl-D-aspartate (NMDA) glutamate receptor s in the transmission of gastrointestinal satiety signals at the level of t he nucleus of the solitary tract (NTS), we assessed the effect of fourth ve ntricular infusion of the noncompetitive NMDA receptor antagonist MK-801 on shortterm sucrose intake and on gastric distension-induced Fos expression in the dorsal vagal complex of unanesthetized rats. MK-801, although not af fecting initial rate of intake, significantly increased sucrose intake duri ng the later phase of the meal (10-30 min, 8.9 +/- 1.0 vs. 2.9 +/- 0.8 ml, P < 0.01). In the medial subnucleus of the NTS, the area postrema, and the dorsal motor nucleus, MK-801 did not reduce gastric distension-induced Fos expression and itself did not significantly induce Fos expression. In the d orsomedial, commissural, and gelatinosus subnuclei, MK-801 in itself produc ed significant Fos expression and significantly reduced (-75%, P < 0.05) th e ability of gastric distension to induce Fos expression, assuming an addit ive model with two separate populations of neurons activated by distension and the blocker. Although these results are consistent with NMDA receptor-m ediated glutamatergic transmission of vagal satiety signals in general, the y lend limited support for such a role in the transmission of specific gast ric distension signals.