Abstract # 1853 Behaviorally conditioning of anti-proliferative and immosuppressive effects with rapamycin

Abstract

We established a model of behaviorally conditioned immunosuppression using a conditioned taste aversion (CTA) paradigm in rats, pairing a novel taste (saccharin) as a conditioned stimulus (CS) with the immunosuppressive drug cyclosporine A (CsA) as unconditioned stimulus (US). By re-presenting the CS during retrieval, rats avoid drinking the saccharin and concomitantly displaying immunosuppression reflected by a reduction in splenic T-cell IL-2 production. However, since treatment of with calcineurin inhibitors such as CsA does only apply to some diseases, the employment of this learning protocol of behaviorally conditioned immunosuppression with CsA as supportive therapy together with standard pharmacological regimes in clinical situations has its limitations. Thus, the present study analyzed the capability of our CTA paradigm to behaviorally condition anti-proliferative and immunosuppressive effects of rapamycin (RAPA), an inhibitor of the mTOR-signaling pathway, which is widely used as anti-tumor medication and for the prevention of acute graft rejection. Behavioral conditioning with RAPA as an US induced taste aversion, a suppression of IL-10 cytokine production, as well as a diminished proliferation of CD4 + T-cells. Our results suggest that conditioning of immunosuppressive effects is not just restricted to calcineurin-inhibitors such as CsA but may also apply to other immunomodulating compounds, targeting different signaling pathways.