Serotonergic (5-hydroxytryptamine, 5-HT) neurons of the area postrema (AP) represent one neuronal phenotype implicated in the regulation of salt appetite. Tryptophan hydroxylase (Tryp-OH, synthetic enzyme producing 5-HT) immunoreactive neurons in the AP of rats become c-Fos activated following conditions in which plasma sodium levels are elevated; these include intraperitoneal injections of hypertonic saline and sodium-repletion. Non Tryp-OH neurons also became c-Fos activated. Sodium depletion, which induced an increase in plasma osmolality but caused no significant change in the plasma sodium concentration, had no effect on the c-Fos activity in the AP. Epithelial sodium channels (ENaCs) are expressed in the Tryp-OH immunoreactive AP neurons, possibly functioning in the detection of changes in plasma sodium levels. Since little is known about the neural circuitry of these neurons, we tested one hypothesis and that was whether the AP contributes to a central pathway that innervates the reward center of the brain. Stereotaxic injections of pseudorabies virus were made in the nucleus accumbens (NAc), and after 4 days, this viral tracer produced retrograde transneuronal labeling in the Tryp-OH and non-Tryp-OH AP neurons. Both sets of neurons innervate the NAc via a multisynaptic pathway. Besides sensory information regarding plasma sodium levels, the AP->NAc pathway may also transmit other types of chemosensory information, such as those related to metabolic functions, food intake, and immune system, to the subcortical structures of the reward system. Since these subcortical regions ultimately project to the medial prefrontal cortex, different types of chemical signals from visceral systems may influence affective functions.