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Sabita Roy, PhD; Richard Charboneau; Kelly J. Cain, MS; Rebecca B. Chapin, PhD; Roderick A. Barke, MD

Arch Surg. 1995;130(11):1209-1216.

Abstract
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)

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.

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