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:
Unteroberdörster M, Herring A, Bendix I, Lückemann L, Petschulat J, Sure U, Keyvani K, Hetze S, Schedlowski M, Hadamitzky M. (2021) Neurobehavioral effects in rats with experimentally induced glioblastoma after treatment with the mTOR-inhibitor rapamycin. Neuropharmacol. 184
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, Herring A, Kirchhof J, Bendix I, Haight MJ, Keyvani K, Lückemann L, Unteroberdörster M, Schedlowski M (2018) Repeated Systemic Treatment with Rapamycin Affects Behavior and Amygdala Protein Expression in Rats. Int J Neuropsychopharmacol. 21(6): 592–602.
Hadamitzky M, Lückemann L, Pacheco-López G, Schedlowski M (2020) Pavlovian Conditioning of Immunological and Neuroendocrine Functions. Physiol Rev. 100(1): 357–405.
Hadamitzky M, Orlowski K, Schwitalla JC, Bösche K, Unteroberdörster 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.
Kirchhof J, Petrakova L, Brinkhoff A, Benson S, Schmidt J, Unteroberdörster M, Wilde B, Kaptchuk TJ, Witzke O, Schedlowski M (2018) Learned immunosuppressive placebo responses in renal transplant patients. Proc Natl Acad Sci USA. 115(16): 4223–4227.
Lückemann L, Stangl H, Straub RH, Schedlowski M, Hadamitzky M (2019) Learned immunosuppressive placebo response attenuates disease progression in a rodent model of rheumatoid arthritis. Arthritis Rheumatol. 72(4): 588-597.
Lückemann L, Unteroberdörster M, Martinez Gomez E, Schedlowski M, Hadamitzky M (2019) Behavioral conditioning of anti-proliferative and immunosuppressive properties of the mTOR inhibitor rapamycin. Brain Behav Immun. 79: 326–331.
Pacheco-López G, Niemi M-B, Kou W, Härting M, Fandrey J, Schedlowski M (2005) Neural substrates for behaviorally conditioned immunosuppression in the rat. J Neurosci. 25(9): 2330–2337.