Pro-inflammatory cytokines promote behavioral and neurochemical variations similar to those evident following stressor exposure, and have been implicated in promoting depressive illness. Indeed, immunotherapeutic application of the cytokine, interferon-alpha, promoted depressive illness in cancer and hepatitis C patients. We assessed the possibility that another interferon cytokine family member, interferon-gamma (IFN-γ), might contribute to the behavioral and biochemical alterations provoked by a chronic stressor regimen that has been used to model neuropsychiatric pathology in rodents. As predicted, IFN-γ-deficient mice displayed basal differences in behavior (e.g., reduced open field exploration) and altered neurochemical activity (e.g., increased noradrenergic and serotonergic activity within the central amygdala), relative to their wild-type counterparts. Moreover, stressor-induced elevations of corticosterone and the pro-inflammatory cytokine, tumor necrosis factor-alpha, were attenuated in IFN-γ-deficient mice. Similarly, the IFN-γ null mice were refractory to the chronic stressor-induced alterations of dopamine metabolism (within the prefrontal cortex, paraventricular nucleus of the hypothalamus and central amygdala) evident in wild-type mice. Yet, the chronic stressor provoked signs of anxiety (e.g., reduced open field exploration) and depression-like behavior (e.g., increased forced swim immobility, reduced consumption of a palatable solution) among both wild-type and IFN-γ knockout mice alike, suggesting a dissociation of behavioral functioning from the stressor-induced alterations of immunological, hormonal and dopaminergic activity. Together, these data suggest a complex neurobehavioral phenotype, wherein IFN-γ deletion engenders a state of heightened basal emotionality coupled with increased monoaminergic activity in the amygdala. At the same time, however, IFN-γ deficiency appears to blunt some of the neurochemical, corticoid and cytokine alterations ordinarily associated with chronic stressor exposure.

Additional Metadata
Keywords Anxiety, Behavior, Chronic stress, Cytokine, Depression, Genetic knockout, Monoamine, Neuroendocrine, Neuroinflammatory, Neurotransmitter, Pathology
Persistent URL dx.doi.org/10.1016/j.bbi.2009.12.001
Journal Brain Behavior and Immunity
Citation
Litteljohn, D. (Darcy), Cummings, A. (Amie), Brennan, A. (Ashley), Gill, A. (Anudip), Chunduri, S. (Siri), Anisman, H, & Hayley, S. (2010). Interferon-gamma deficiency modifies the effects of a chronic stressor in mice: Implications for psychological pathology. Brain Behavior and Immunity, 24(3), 462–473. doi:10.1016/j.bbi.2009.12.001