centers, cytokine-specific transport molecules expressed on the brain endothelium, and circumventricular organs (Besedovsky and del Rey, 1996; McAfoose and Baune, 2009; Quan, 2008). Upon reaching the brain, cytokine signals can be amplified through a central cytokine network that has profound effects on neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, and behavior (Dantzer et al., 2008). Thus, it seems likely that LPS acts on TLR4 on peripheral tissues, such as macrophages, liver Kupffer cells or endothelial cells to transiently release cytokines which then act on their receptors in the brain to produce long-lasting changes in neuroimmune function (Qin et al., 2007, 2008). However, there is some evidence that LPS elicits TLR4 signaling in the brain independent of peripheral cytokine responses (Chakravarty and Herkenham, 2005; Gosselin and Rivest, 2008). Regardless of the site of action of LPS, it is likely that this persistent perturbation of neuroimmune signaling is responsible for the changes in dopamine cell firing, CTA, and alcohol consumption that we observed.
