Infusion of neurotoxic doses of N-methyl-D-aspartate into the lateral hypothalamus in rats produces stomach erosions, hyperthermia, and a disruption in eating behavior.

The present study examined whether damage to intrinsic lateral hypothalamic (LH) neurons induced by microinfusions of N-methyl-D-aspartate (NMDA) would produce effects similar to those seen after electrolytic LH lesions. In Experiment 1, rats receiving electrolytic (1.2 mA anodal current, 10 s) LH lesions displayed motor impairments, whereas those receiving NMDA (20 microg/microl) infusions did not. Both electrolytic lesions and NMDA infusions were associated with eating deficits, hyperthermia, and gastric erosion formation 24 hr after surgery. In Experiment 2, either 20 microg/microl or 10 microg/microl NMDA destroyed LH cells and produced dose-dependent gastric mucosal erosions as well as similar increases in body temperature. These results indicate that an alteration in the acute activity of intrinsic LH neurons plays a role in the production of gastric mucosal injury and hyperthermia and lend support to other studies implicating a role of LH neurons in eating behavior.

Gastric mucosal erosion produced by NMDA microinfusions in the lateral hypothalamus: effect of selective knife cuts.

Bilateral infusions of N-methyl-D-aspartate (NMDA) into the lateral hypothalamus (LH) produce gastric erosions in rats. The present study attempted to determine the neural pathways that mediate this effect. In order to interrupt axonal transmission, knife cuts (KC) were made in different planes adjacent to the LH. In separate groups of rats, KC were made anterior, posterior or lateral to the LH just prior to bilateral NMDA infusions (20 micrograms/microliter). The incidence of gastric erosions was measured 24 h after NMDA infusions. Animals receiving sham KC and infused with NMDA exhibited significantly more gastric erosions than those infused with vehicle. Lateral parasagittal KC blocked the occurrence of gastric erosions produced by NMDA, whereas anterior coronal KC significantly increased the incidence of erosions produced by NMDA. Posterior coronal KC did not alter the incidence of gastric erosions produced by NMDA infusions into the LH. These results suggest that intrinsic LH neurons with gastric function project axons laterally and probably descend through the internal capsule to brainstem medullary nuclei. The results of the anterior KC suggest that the LH sends and/or receives inhibitory projections from neural structures (possibly the amygdaloid complex) anterior to the plane of the KC.