Recent findings have suggested that the
N-methyl-D-aspartate (
NMDA) receptor-dependent
hydroxyl radical pathway in the hypothalamus of rabbit brain may mediate the
fever induced by
lipopolysaccharide (LPS). The aim of this study was to investigate whether
aspirin exerts its antipyresis by suppressing hypothalamic
glutamate and
hydroxyl radicals in rabbits. The microdialysis probes were stereotaxically and chronically implanted into the preoptic anterior hypothalamus of rabbit brain for determination of both
glutamate and
hydroxyl radicals in situ. It was found that intravenous (i.v.) injection of LPS, in addition to inducing
fever, caused increased levels of both
glutamate and
hydroxyl radicals in the hypothalamus. Pretreatment with
aspirin (10 - 60 mg/kg, i.v.) one hour before an i.v. dose of LPS significantly reduced the febrile response and attenuated the LPS-induced increased levels of both
glutamate and
hydroxyl radicals in the hypothalamus. The increased levels of
prostaglandin E(2) (
PGE(2)) in the hypothalamus induced by LPS could be suppressed by
aspirin pretreatment. The data indicate that systemic administration of
aspirin, in addition to suppressing
PGE(2) production, may exert its antipyresis by inhibiting the
NMDA receptor-dependent
hydroxyl radical pathways in the hypothalamus during LPS
fever.