NMDA receptor coagonist glycine site: evidence for a role in lateral hypothalamic stimulation of feeding.

To investigate the role of the glycine coagonist binding site on the N-methyl-D-aspartate (NMDA) receptor in feeding control, we injected the glycine site antagonist 7-chlorokynurenic acid (7-CK) into the lateral hypothalamus (LH) of satiated rats before LH injection of NMDA, 7-CK (10-44 nmol) blocked the 6- to 10-g eating response elicited by NMDA. This block was reversed by LH pretreatment with glycine, arguing for a specific action at the glycine site. In contrast to the suppression produced by high doses, 7-CK at 0.1 nmol enhanced NMDA-elicited eating. For examination of behavioral specificity, 7-CK was injected into the LH before kainic acid (KA) or DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA). 7-CK at a dose of 0.1 nmol suppressed feeding elicited by KA or AMPA, but at 10 nmol it suppressed eating elicited by AMPA while enhancing eating elicited by KA. Finally, bilateral LH injection of 7-CK effectively suppressed eating produced by fasting. These findings support a role for the NMDA receptor coagonist glycine site in LH regulation of eating behavior.