How does immune challenge inhibit ingestion of palatable food? Evidence that systemic lipopolysaccharide treatment modulates key nodal points of feeding neurocircuitry.

Immune challenge induces behavioral changes including reduced ingestion of palatable food. Multiple pathways likely contribute to this effect, including viscerosensory pathways controlling hypothalamic feeding circuits or by influence on "reward" circuitry previously established to control ingestive behavior. To investigate whether the effects of immune challenge may influence this network, we compared brain activation patterns in animals trained to drink a palatable sweetened milk solution and treated systemically with either the immune stimulant lipopolysaccharide (LPS) or saline. Brain sections were processed for localization of the activation marker c-Fos in neurons of regions implicated in regulation of feeding behavior. Sweetened milk ingestion was associated with increased numbers of c-Fos positive neurons in the caudal core and shell of the nucleus accumbens (NAc), the paraventricular thalamus (PVT), central nucleus of the amygdala (CEA), the basal lateral amygdala (BLA), in orexin-A containing neurons of the lateral hypothalamus (LH), and in cocaine and amphetamine regulated transcript (CART) neurons of the arcuate hypothalamus. In LPS-treated animals sweetened milk consumption was significantly reduced, as was c-Fos induction in the hypothalamic orexin-A and CART neurons, and in the BLA. In addition, induction of c-Fos in the rostral regions of the NAc, the PVT, and CEA was increased following LPS treatment, compared to controls. The findings from this study point to a network of brain regions (LH, PVT, NAc, and BLA) previously implicated in the modulation of feeding behavior, reward, and arousal that may also contribute to neural substrates involved in the reorganization of behavioral priorities that occurs during sickness.