Grant: Discovery Grants Program - Individual

Stressful events may promote the development and exacerbation of psychological, as well as immunologically based illnesses. While the psychological changes may involve alterations of central transmitter activity, physical illnesses may stem from transient immunological and neuroendocrine effects of the stressor, thereby influencing the organism's ability to contend with pathogens.  Interestingly, it seems that not only do stressors or CNS events influence immune functioning, but immunological alterations may come to affect central neurotransmitter activity. Indeed, immune activation may profoundly affect central neurochemical functioning (including effects on norepinephrine, serotonin and dopamine, as well as corticotropic releasing hormone, and its receptors subtypes), and such effects may interact with stressors. Given the profile of neurochemical and hormonal changes observed following antigenic challenge, it was suggested that the immune system may act as a sensory organ informing the CNS of the presence of viral or bacterial challenge (which may be translated translated as a stressor).  The proposed studies will assess the conditions wherein stressors impact on immune functioning, with particular reference to the time course of the changes induced by stressors and the influence of chronic, unpredictable stressors (of moderate severity) that appreciably increase allostatic overload. The immune changes will be related to stressor provoked neuroendocrine and neurotransmitter changes (including monoamines and neuropeptides), and studies will assess the effects of specific neurochemical manipulations on stressor provoked immune alterations. In addition, experiments will assess the proactive effects of the stressors (sensitization effects with respect to behavior and neurochemical functioning) in response to later stressor or immune challenges. Finally, given that immune activation may influence affective state, the effects of stressors and immune challenges will be assessed in behavioral tests thought to mimic anxiety and depressive illness. Once again the effects of manipulations that affect CRH or monoamine functioning will be determine whether these modify immune-provoked behavioral disturbances.