Anhedonic and Anxiogenic Effects of Cytokine Exposure

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Abstract
It is abundantly clear that interactions occur between the immune, endocrine, central, and autonomic nervous systems. Immunologic manipulations (or products of an activated immune system, e.g., cytokines) affect neuroendocrine and central neurotransmitter processes, and conversely, neuroendocrine and central neurotransmitter alterations may impact on immune activity (Anisman, Zalcman, & Zacharko, 1993; Blalock, 1994; Dunn, 1990; Rivier, 1993; Rothwell & Hopkins, 1995). It has been posited that, among other things, the immune system acts like a sensory organ informing the brain of antigenic challenge (Blalock, 1984, 1994). Furthermore, given the nature of the neurochemical changes elicited by antigens and cytokines, it was suggested that immune activation may be interpreted by the CNS as a stressor (Anisman et al., 1993; Dunn, 1990; Dunn, Powell, Meitin, & Small, 1989). To be sure, the effects of systemic Stressors (e.g., those associated with viral insults, bacterial endotoxins, cytokines) are not entirely congruous with those elicited by processive stressors (i.e., those involving higher-order sensory processing, e.g., fear conditioning, exposure to a predator or novel environment) (Herman & Cullinan, 1997). Nevertheless, cytokines may be part of a regulatory loop that, by virtue of effects on CNS functioning, might influence behavioral outputs and may even contribute to the symptoms of behavioral pathologies, including mood and anxiety-related disorders (Anisman et al., 1993; Crnic, 1991). It is curious that while cytokines have found an increasingly greater role in immunotherapy, and may contribute to neurodegenerative processes (Rothwell, Luheshi, & Toulmond, 1996), limited attention has been devoted to behavioral analyses of these cytokines in animal studies.