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 m echanism may regulate hepatic c-fos and c-jun gene expression followin g peritoneal sepsis. Methods: First, dopamine or vehicle was instilled into a stereotaxically placed intracerebral-ventricular (ICV) cannula with or without D-1 (SCH 23390) or D-2 (haloperidol) antagonist pretr eatment in a rat model, and the effect on hepatic c-fos or c-jun prote in expression was investigated. Second, we investigated the effect of haloperidol and vehicle treatment following cecal ligation and punctur e (CLP)-induced sepsis with respect to hepatic c-fos protein expressio n, c-jun protein expression, and survival. Results: Intracerebral-vent ricular dopamine treatment increased hepatic c-fos immunoreactive prot ein but had no effect on hepatic c-jun immunoreactive protein expressi on. Pretreatment with SCH 23390 inhibited ICV dopamine treatment-induc ed hepatic c-fos immunoreactive protein expression. Haloperidol pretre atment synergized with ICV dopamine treatment to overexpress hepatic c -fos protein. Haloperidol treatment significantly increased CLP-induce d hepatic c-fos and c-jun protein expression and improved survival fol lowing CLP. Conclusions: Hepatic c-fos protein expression may be regul ated, in part, by a central nervous system-mediated dopaminergic D-1 r eceptor mechanism. Treatment with the D-2 receptor antagonist, haloper idol, increases sepsis-induced hepatic c-fos and c-jun protein express ion and improves survival following peritoneal contamination.