Sepsis is defined as the host's reaction to infection and it is characterized by a systemic inflammatory response with important clinical implications. Central nervous system dysfunction secondary to sepsis is associated with local generation of pro- and anti-inflammatory cytokines, impaired cerebral microcirculation, disturbance of neurotransmitters, apoptosis and cognitive impairment. It is known that during the process of learning and memory formation several pathways are involved such as dopaminergic and cholinergic systems. Thus, the objective of this study is to evaluate the Neuronal calcium sensor (NCS-1) and dopamine-cAMP regulated phosphoprotein of 32,000 kDa (DARPP-32) expression as well as Brain-derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) levels in prefrontal cortex and hippocampus of rats 12, 24 and 48 hours after sepsis induction. To this aim, we used sham-operated Wistar rats or submitted to the cecal ligation and perforation procedure. After 12 and 24 hours, there was an increase of NGF levels in hippocampus; and up to 48 hours, a decrease of NCS-1 expression in prefrontal cortex, a decrease of BDNF levels in hippocampus and an increase of NGF levels in hippocampus. In conclusion, we believe that the low expression of NCS-1 in prefrontal cortex and low levels of BDNF in hippocampus may be associated with the pathophysiology of cognitive impairment during sepsis and a putative role of the dopaminergic system. Synapse, 2014. © 2014 Wiley Periodicals, Inc.