TNF-alpha-induced c-Fos generation in the nucleus of the solitary tract isblocked by NBQX and MK-801

Previous studies have shown that identified neurons of the nucleus of the s olitary tract (NST) are excited by the cytokine tumor necrosis factor-alpha (TNF-alpha). Vagal afferent connections with the NST are predominantly glu taminergic. Therefore, we hypothesized that TNF-alpha effects on NST neuron s may be via modulation of glutamate neurotransmission. The present study u sed activation of the immediate early gene product c-Fos as a marker for ne uronal activation in the NST. c-Fos expression was evaluated after microinj ections of TNF-alpha in the presence or absence of either the alpha -amino- 3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist 1,2,3,4- t etrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium (NBQ X) or the N-methyl-D-aspartate (NMDA) antagonist MK-801. To assess the spec ificity of the interaction between TNF-alpha and glutamate, c-Fos expressio n was also evaluated after injection of oxytocin (OT) (which has a direct e xcitatory effect in this area of the brain stem) in the presence and absenc e of NBQX or MK-801. c-Fos labeling was significantly increased in the NST after TNF-alpha exposure. Coinjection of either NBQX or MK-801 with TNF-alp ha prevented significant c-Fos induction in the NST. Microinjections of OT also induced significant NST c-Fos elevation, but this expression was unaff ected by coinjection of either antagonist with OT. These data lead us to co nclude that TNF-alpha activation of NST neurons depends on glutamate and su ch an interaction is not generalized to all agonists that act on the NST.