Lesions of the dorsal vagal complex abolish increases in meal size induced by NMDA receptor blockade.

Rats increase meal size and duration after intraperitoneal injection of MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. This effect depends upon intact vagal fibers, since the antagonist does not increase intake when visceral afferent and efferent pathways have been interrupted by bilateral subdiaphragmatic vagotomy. NMDA receptors have been demonstrated on vagal afferent fibers and on second-order neurons in the medial subnucleus of the solitary tract (NTS), the area postrema (AP), and the dorsal motor nucleus of the vagus. To determine whether neurons in these structures are crucial for NMDA receptor effects on feeding, we examined the effect of MK-801 on intake of 15% sucrose in rats with aspiration lesions of the AP and adjacent NTS. MK-801 (100 microg/kg, i.p.) significantly increased sucrose intake in these lesioned rats compared to sham-lesioned rats (32.3+/-0.1 ml versus 23.3+/-0.1 ml, P<0.001). However, when the AP/NTS aspiration lesions were combined with bilateral electrolytic destruction of the medial NTS and the DMV, lesioned rats consumed nearly the same amount of sucrose after either saline or MK-801 (25.9+/-2.4 ml versus 24.3+/-3. 0 ml; P=0.687). By contrast, sham-lesioned controls ingested significantly more sucrose following MK-801 compared to saline (19. 8+/-1.0 ml versus 13.1+/-0.8 ml, P<0.001). These results suggest that an intact caudomedial NTS and/or DMV are necessary for increases in intake induced by NMDA receptor blockade. While the AP might participate in MK-801-induced enhancement of intake, it is not essential for this effect.