Based on our established taste-immune paradigm in rats employing the immunosuppressive drug cyclosporine A (CsA), we will investigate extinction and reconsolidation of behavioral conditioned immune responses of immunomodulating compounds with distinct cell signaling pathways (rapamycin, methotrexate), Moreover, we will employ DREADDs to analyze the role of brain structures steering these learning processes, and will analyze the potential clinical relevance of learned immunomodulation employing a tumor model as well as a model of chronic inflammatory autoimmune disease.
Guiding questions of A18:
- Are learned immune responses restricted to calcineurin inhibitors such as CsA or does conditioning with other immunomodulating drugs and distinct cell signaling pathways such as RAPA or MTX operate under similar mechanisms?
- Which brain areas mediate learning and extinction processes of conditioned immunopharmacological effects?
- Can extinction of the learned immunopharmacological effects of RAPA and MTX be inhibited by administering sub- or low-therapeutic drug doses during retrieval as reminder cues concomitantly with the CS?
- Are behaviorally conditioned anti-proliferative (RAPA) and anti-metabolic effects (MTX) of clinical relevance by interfering with disease progression in animal models of tumor growth and inflammatory autoimmune diseases?