Antipyretic effect of acetaminophen by inhibition of glutamate release after staphylococcal enterotoxin A fever in rabbits.

The present study was designed to determine whether the inhibition of glutamate release in organum vasculosum laminae terminalis (OVLT) of rabbit brain by acetaminophen might be protective in a whole-animal model of staphylococcal enterotoxin A (SEA) fever. Unanesthetized rabbits were administered intravenously with SEA, and both colonic temperature (Tco) and glutamate release in OVLT were measured simultaneously. The glutamate release in OVLT was measured with a microdialysis probe previously implanted. Both the Tco and glutamate release in OVLT were simultaneously increased following intravenous administration of SEA. The SEA-induced rise in both the Tco and the levels of glutamate release in OVLT were suppressed by pretreatment with intravenous injection of acetaminophen (1, 5 or 10 mg/kg). Furthermore, treatment of OVLT with acetaminophen (50-150 microg) attenuated the fever-like hyperthermia induced by intra-OVLT injection of glutamate. Our results show acetaminophen may reduce glutamate release in OVLT and result in antipyresis.