Murine taste-immune associative learning.

Taste-immune associative learning can result from contingent pairings of an immune-competent unconditioned stimulus (US) with a gustative conditioned stimulus (CS). Recalling such an association may induce a set of physiological responses affecting behavior, endocrine, and immune functions. We have established a model of behaviorally conditioned immunosuppression employing the immunosuppressant drug cyclosporine A (CsA) as the US and saccharin as the CS in rats and humans. In order to investigate the inter-species generalization of this neuro-immune interaction, we tested the feasibility of this paradigm in mice. In a single-bottle scheme, male BALB/c mice (n=5) were conditioned by conducting three association trials and a single recall trial. Control groups (n=5/group) were designed to assure associative learning, pharmacological effects of the US, and placebo effect. Results show that CsA-conditioned animals displayed significant immunosuppression in the spleen after recall, measured by in vitro T-lymphocyte proliferation, and IL-2 production. However, the same animals did not show evidence of avoidance behavior to the CS. In contrast, evoking the association of saccharin-lithium chloride (inducing gastric malaise) in another set of animals (n=4/group) resulted in significant and pronounced avoidance of the taste (CS). These animals also displayed significant suppression of splenic T-lymphocyte responsiveness after the recall phase. The present results indicate that mice seem to be capable of associating a gustative stimulus with CsA, resulting in behaviorally conditioned immunosuppression without affecting appetitive behavior.