Origins of lateral hypothalamic afferents associated with N-methyl-d-aspartic acid-elicited eating studied using reverse microdialysis of NMDA and Fluorogold

Abstract

Afferent projections to the tuberal lateral hypothalamus (tLH), where excitatory amino acid application is most effective in eliciting feeding, and to the anterior, posterior and medial regions of the hypothalamus were studied using reverse microdialysis of N-methyl-D-aspartic acid (NMDA) and Fluorogold (FG). NMDA at 660 microM delivered for 10 min was effective in stimulating food intake only when administered into the tLH, causing a mean intake of 9.3 g compared to less than 1 g in any other site. Subsequent administration of FG through the dialysis probe retrogradely in labeled neurons in brain structures associated with the feeding response including the frontal cortex, amygdala, nucleus accumbens (NA), preoptic areas, substantia nigra, ventral tegmental area (VTA), parabrachial nucleus, and the nucleus of the solitary tract (NST). Labeling after anterior and posterior LH infusion of FG was similar to that seen after tLH delivery with some apparent differences, whereas FG administration into the medial hypothalamus produced a distinctly different pattern of labeling compared to the other groups. Some of the observed labeling appeared to be almost exclusively associated with the tLH where NMDA elicits feeding. In particular, amygdala, preoptic area and shell of the accumbens labeling was noticeably denser in tLH eaters than in all other groups. These findings are consistent with the role of LH glutamate and NMDA receptors in the regulation of food intake and identify afferents to the region which possibly mediate endogenous LH glutamate's effects on feeding.