BEHAVIORAL NEUROSCIENCE REVIEW ARTICLE

and sophisticated interactions occur among these cells, primarily via soluble protein messengers called cytokines. Important for this review, bidirectional communication between the brain and immune system by cytokines has signifi cant consequences for behavior. For instance, sick animals exhibit several well- characterized behavioral changes, including reductions in food and water intake, activity, exploration, and social and sexual interactions (Hart, 1988; Kent et al., 1992). Importantly, these so-called “sickness behaviors ” are not mediated by the infectious pathogens themselves, but rather are orchestrated by the host via cytokines (Dantzer and Kelley, 2007). Numerous studies have now demonstrated that these behaviors are organized, adaptive strategies that are critical to host survival (Dantzer and Kelley, 2007; Nesse and Williams, 1994). Thus, sick-ness behavior refl ects an overall change in the motivational state of the individual that is organized by both the nervous and the immune systems. We believe that cytokines are important not only for behavio-ral changes during acute illness, but may also underlie long-term changes in behavior as a consequence of infection early in life. Thus, the purpose of this review is to: (1) summarize the evidence that infections occurring during the perinatal period can produce effects on brain and subsequent behavior that endure through-out an organism’s life span, and (2) discuss the potential role of cytokines and glia in these long-term changes. Cytokines are pro-duced within the brain during normal brain development, but are expressed at much higher levels during the course of an immun