November 1995

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

Author Affiliations

From the Departments of Surgery (Drs Roy, Chapin, and Barke, Mr Charboneau, and Ms Cain), Pharmacology (Dr Roy), and Food Science and Nutrition (Dr Barke), University of Minnesota, Minneapolis, and the Minneapolis Veterans Administration Hospital.

Arch Surg. 1995;130(11):1209-1216. doi:10.1001/archsurg.1995.01430110067012

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)