Memory reconsolidation prevents extinction of learned immunosuppression

• Published in: Brain, behavior, and immunity Vol. 49; pp. e7 - e8
• Main Authors: Schedlowski, M, Hadamitzky, M, Boesche, K, Lueckemann, L, Engler, H
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-10-2015
• Subjects: Allergy and Immunology; Psychiatry
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2015.06.047

When memories are recalled, they enter a transient labile phase in which they can be impaired or enhanced followed by a new stabilization process termed reconsolidation. It is unknown, however, whether reconsolidation is restricted to neurocognitive processes such as fear memories or can be extended to peripheral physiological functions as well. Bidirectional interaction between the brain and peripheral immune system, together with the fact that immune functions can be modified by associative learning processes provide a unique opportunity to test this assumption. Employing an established paradigm of behaviorally-conditioned taste aversion in rats, we here demonstrate reconsolidation in “learned immunosuppression”. The administration of sub-therapeutic doses of the calcineurin inhibitor and immunosuppressant cyclosporin A (CsA) together with the conditioned stimulus (CS/saccharine) during evocation blocked the extinction of conditioned taste aversion and learned suppression of T cell cytokine (interleukin-2; interferon-gamma) production. In contrast, reconsolidation of learned immunosuppression could not be induced by administering sub-therapeutic CsA as a reminder cue outside the reconsolidation window, 8 hours after CS exposure. This reconsolidated immunosuppression is of clinical relevance since it significantly prolonged the survival time of heterotopically-transplanted heart allografts in rats. Collectively, these findings demonstrate that memories can reconsolidate on peripheral physiological systems such as immune functioning; they might pave the way for the systematic integration of conditioning paradigms as supportive therapy in pharmacological regimens.