Mediation of the extinction process in behaviorally conditioned immunosuppression

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To analyze neuro-immune-communication, our research group established a model of conditioned immunosuppression in rats which follows the principle of classical (Pavlovian) conditioning. We employed a conditioned taste aversion (CTA) paradigm where the novel taste saccharin (conditioned stimulus/CS) is paired with the immunosuppressive drug cyclosporine A (unconditioned stimulus/US). Upon re-exposure to the conditioned stimulus animals show a reduced CTA (saccharine intake), as well as a significant inhibition of T lymphocyte proliferation and IFN-γ and IL-2 in anti-CD3 stimulated splenic T cells. Repeated, unreinforced re-exposure to the CS leads to an extinction of the conditioned behavioral (CTA) and immune responses (cytokine inhibition, lymphocyte proliferation). In order to analyze the neurobiological mechanisms responsible for the extinction process we administered the protein synthesis inhibitor Anisomycin, or the beta-adrenergic receptor blocker Propranolol into the insular cortex during evocation, as the insular cortex is known to mediate the learned immune response during re-exposure of the CS. Our preliminary data show a prolonged extinction of the CTA reflected by a reduced CS intake after micro injection of protein synthesis inhibitor Anisomycin but not after administration of Propranolol into the insular cortex. Ongoing experiments will reveal whether the prolonged extinction on the behavioral level can also be detected in the conditioned immune response.