GLUTAMATE RECEPTORS IN THE RAT HYPOTHALAMUS AND PITUITARY

Although several recent anatomical and physiological studies indicate that glutamate receptors are likely to play a role in the regulation o f various hypothalamic functions, no attempt has yet been made to spec ifically characterize glutamate receptor densities, subtypes, or local ization in the hypothalamus. To provide this basic information, we hav e characterized and mapped the binding of [H-3]glutamate to N-methyl-D -aspartate (NMDA), non-NMDA, and metabotropic glutamate receptors thro ughout the diencephalon. Membrane binding assays revealed a [H-3]gluta mate binding density of 2.6 pmol/mg protein, approximately one third o f the hippocampal density. Binding of subtype-specific agonists and an tagonists was complex, but clearly indicated that each major glutamate subtype is present in all hypothalamic and preoptic regions in the fo llowing approximate relative densities: NMDA > metabotropic Glu recept or > kainate greater than or equal to lpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid. Receptor autoradiography confirmed the widesp read presence of all major glutamate receptor subtypes with roughly th e following relative regional densities: ventromedial, dorsomedial > p araventricular, anterior hypothalamic, supraoptic > arcuate, suprachia smatic, lateral hypothalamic > preoptic area much greater than pituita ry neural lobe, white matter > pituitary anterior lobe (negligible). S ubtype expression varied regionally, with rostral hypothalamic and pre optic regions having proportionally higher levels of non-NMDA vs. NMDA binding. High densities of glutamate receptors in ventromedial and me dial hypothalamic regions suggest a prominent role in neuroendocrine a nd autonomic regulation.