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:
Hadamitzky M, Bösche K, Engler A, Schedlowski M, Engler H (2015) Extinction of conditioned taste aversion is related to the aversion strength and associated with c-fos expression in the insular cortex. Neuroscience. 303: 34–41.
Hadamitzky M, Bösche K, Wirth T, Buck B, Beetz O, Christians U, Schniedewind B, Lückemann L, Güntürkün O, Engler H, Schedlowski M (2016) Memory-updating abrogates extinction of learned immunosuppression. Brain Behav Immun. 52: 40–48.
Hadamitzky M, Engler H, Schedlowski M (2013) Learned immunosuppression: extinction, renewal, and the challenge of reconsolidation. J Neuroimmune Pharmacol. 8(1): 180–188.
Hadamitzky M, Orlowski K, Schwitalla JC, Bösche K, Unteroberdorster M, Bendix I, Engler H, Schedlowski M (2016) Transient inhibition of protein synthesis in the rat insular cortex delays extinction of conditioned taste aversion with cyclosporine A. Neurobiol Learn Mem. 133: 129–135.
Lückemann L, Bösche K, Engler H, Schwitalla J-C, Hadamitzky M, Schedlowski M (2016) Pre-exposure to the unconditioned or conditioned stimulus does not affect learned immunosuppression in rats. Brain Behav Immun. 51: 252–257.
Pacheco-Lopez G, Niemi M-B, Kou W, Harting M, Fandrey J, Schedlowski M (2005) Neural substrates for behaviorally conditioned immunosuppression in the rat. J Neurosci. 25(9): 2330–2337.
Pacheco-Lopez G, Riether C, Doenlen R, Engler H, Niemi M-B, Engler A, Kavelaars A, Heijnen CJ, Schedlowski M (2009) Calcineurin inhibition in splenocytes induced by pavlovian conditioning. FASEB J. 23(4): 1161–1167.
Schedlowski M, Enck P, Rief W, Bingel U (2015) Neuro-Bio-Behavioral Mechanisms of Placebo and Nocebo Responses: Implications for Clinical Trials and Clinical Practice. Pharmacol Rev. 67(3): 697–730.
Schedlowski M, Pacheco-Lopez G (2010) The learned immune response: Pavlov and beyond. Brain Behav Immun. 24(2): 176–185.
Tuerkmen A, Bösche K, Lückemann L, Engler H, Schedlowski M, Hadamitzky M (2016) Rats taste-aversive learning with cyclosporine a is not affected by contextual changes. Behav Brain Res. 312: 169–173.