Lesions of the dorsal vagal complex abolish increases in meal size inducedby 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. Thi s effect depends upon intact vagal fibers, since the antagonist does not in crease intake when visceral afferent and efferent pathways have been interr upted by bilateral subdiaphragmatic vagotomy. NMDA receptors have been demo nstrated on vagal afferent fibers and on second-order neurons in the medial subnucleus of the solitary tract (NTS), the area postrema (AP), and the do rsal motor nucleus of the vagus. To determine whether neurons in these stru ctures are crucial for NMDA receptor effects on feeding, we examined the ef fect of MK-801 on intake of 15% sucrose in rats with aspiration lesions of the AP and adjacent NTS. MK-801 (100 mu g/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 aspirati on lesions were combined with bilateral electrolytic destruction of the med ial NTS and the DMV, lesioned rats consumed nearly the same amount of sucro se after either saline or MK-801 (25.9+/-2.4 ml versus 24.3+/-3.0 ml; P=0.6 87). By contrast, sham-lesioned controls ingested significantly more sucros e 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 a re necessary for increases in intake induced by NMDA receptor blockade. Whi le the AP might participate in MK-801-induced enhancement of intake, it is not essential for this effect. (C) 2000 Elsevier Science B.V. All rights re served.