Modulation of lipopolysaccharide-induced tumor necrosis factor-α and nitric oxide production by dopamine receptor agonists and antagonists in mice

The effects of various agonists and antagonists of dopamine D₁ and D₂ receptors on lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) and nitric oxide (NO) production was investigated in mice. Pretreatment of animals with bromocryptine or quinpirole, agonists of dopamine D₂ receptors caused a blunting of both the TNF-α and MO responses to LPS injected intraperitoneally. Sulpiride, an antagonist of dopamine D₂ receptors, decreased the LPS-induced TNF-α plasma levels in a dose-dependent manner and inhibited the LPS-induced NO production by peritoneal macrophages. Bromocryptine or quinpirole blunted both the TNF-α and NO response to LPS. SCH-23390, an antagonist of dopamine D₁ receptors did not alter LPS-induced TNF-α production, but inhibited LPS-induced NO production. These results indicate that while the D₂ subtype of dopamine receptors is involved in the modulation of both LPS-induced TNF-α and NO production, dopamine D₁ receptors only regulate the production of NO. Since several drugs possess effect on dopamine D₂ receptors, the present observations may be of clinical relevance.