The Possible Role of a Central Nervous System Dopaminergic Mechanism in Hepatic c-fos Protein Expression Following Peritoneal Sepsis

Objective:  To investigate the hypothesis that a central dopaminergic mechanism may regulate hepatic c-fos and c-jun gene expression following peritoneal sepsis.

Methods:  First, dopamine or vehicle was instilled into a stereotaxically placed intracerebral-ventricular (ICV) cannula with or without D₁ (SCH 23390) or D₂ (haloperidol) antagonist pretreatment in a rat model, and the effect on hepatic c-fos or c-jun protein expression was investigated. Second, we investigated the effect of haloperidol and vehicle treatment following cecal ligation and puncture (CLP)–induced sepsis with respect to hepatic c-fos protein expression, c-jun protein expression, and survival.

Results:  Intracerebral-ventricular dopamine treatment increased hepatic c-fos immunoreactive protein but had no effect on hepatic c-jun immunoreactive protein expression. Pretreatment with SCH 23390 inhibited ICV dopamine treatment–induced hepatic c-fos immunore-active protein expression. Haloperidol pretreatment synergized with ICV dopamine treatment to overexpress hepatic c-fos protein. Haloperidol treatment significantly increased CLP-induced hepatic c-fos and c-jun protein expression and improved survival following CLP.

Conclusions:  Hepatic c-fos protein expression may be regulated, in part, by a central nervous system—mediated dopaminergic D₁ receptor mechanism. Treatment with the D₂ receptor antagonist, haloperidol, increases sepsis-induced hepatic c-fos and c-jun protein expression and improves survival following peritoneal contamination.(Arch Surg. 1995;130:1209-1216)