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- Title
Calcineurin inhibition in splenocytes induced by pavlovian conditioning.
- Authors
Pacheco-López, Gustavo; Riether, Carsten; Doenlen, Raphael; Engler, Harald; Niemi, Maj-Britt; Engler, Andrea; Kavelaars, Annemieke; Heijnen, Cobi J.; Schedlowski, Manfred
- Abstract
Pavlovian conditioning is one of the major neurobiological mechanisms of placebo effects, potentially influencing the course of specific diseases and the response to a pharmacological therapy, such as immunosuppression. In our study with behaviorally conditioned rats, a relevant taste (0.2% saccharin) preceded the application of the immunosuppressive drug cyclosporin A (CsA), a specific calcineurin (CaN) inhibitor. Our results demonstrate that through pavlovian conditioning the particular pharmacological properties of CsA can be transferred to a neutral taste, i.e., CaN activity was inhibited in splenocytes from conditioned rats after reexposure to the gustatory stimulus. Concomitant immune consequences were observed on ex vivo mitogenic challenge (anti-CD3). Particularly, Th1-cytokine, but not Th2-cytokine, production and cell proliferation were impeded. Appropriate pharmacological and behavioral controls certify that all these changes in T-lymphocyte reactivity are attributable to mere taste reexposure. Furthermore, the underlying sympathetic-lymphocyte interaction was revealed modeling the conditioned response in vitro. CAN activity in CD4+ T lymphocytes is reduced by β-adrenergic stimulation (terbutaline), with these effects antagonized by the β-adrenoreceptor antagonist nadolol. In summary, CAN was identified as the intracellular target for inducing conditioned immunosuppression by CsA, contributing to our understanding of the intracellular mechanisms behind "learned placebo effects."
- Subjects
CLASSICAL conditioning; TASTE; CYCLOSPORINE; T cells; BETA adrenoceptors; IMMUNOSUPPRESSION
- Publication
FASEB Journal, 2009, Vol 23, Issue 4, p1161
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.08-115683