The regulation of feeding and drinking in rats with lesions of the lateral hypothalamus made by N-methyl-D-aspartate.

Rats bearing excitotoxic lesions of the lateral hypothalamus are hypodipsic and hypophagic, but responses to 24 h food or water deprivation are normal, as are responses to different taste stimuli. The most striking deficit present in lateral hypothalamic-lesioned rats is an inability to respond as controls to dehydrating, dipsogenic or glucoprivic challenges. The present experiments examined the ability of rats bearing bilateral N-methyl-D-aspartate-induced lesions of the lateral hypothalamus to recognize and respond to changes in their internal environments. All of the lesioned rats tested showed mild to moderate hypophagia and hypodipsia, and none responded properly by drinking over 1 h after i.p. injection of hypertonic saline. However, the addition of glucose to the water supply promoted an increase in drinking and a decrease in lab chow consumption to maintain a constant energy intake; the addition of salt to the diet promoted an increase in drinking and no change in eating; 24 h water deprivation induced the same amount of drinking in lateral hypothalamic-lesioned rats as in controls; and injection i.p. of water (but not physiological saline) before drinking water was returned to rats which were 24 h water deprived suppressed drinking. These data suggest that lateral hypothalamic-lesioned rats are in receipt of normal information from their peripheries, and that they can adjust their behaviour over a period of days or minutes to changes in the internal milieu. The most consistent deficit is in responding actively and rapidly to challenging stimuli; the nature of this and the mechanisms which might produce it are discussed. We suggest that the consequences of excitotoxic lesion are better explained by disruption of input to the cortex from the lateral hypothalamus rather than by interference with metabolic processes.