title: Murine taste-immune associative learning.
abstract: 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.
authors.affiliation: Institute for Behavioral Sciences, ETH Zurich, Zurich 8092, Switzerland.
authors.forename: Maj-Britt
authors.initials: MB
authors.lastname: Niemi
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pacheco-López
authors.forename: Wei
authors.initials: W
authors.lastname: Kou
authors.forename: Margarete
authors.initials: M
authors.lastname: Härting
authors.forename: Adriana
authors.initials: A
authors.lastname: del Rey
authors.forename: Hugo O
authors.initials: HO
authors.lastname: Besedovsky
authors.forename: Manfred
authors.initials: M
authors.lastname: Schedlowski
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000187:drug effects / Q000502:physiology*; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D002452:Cell Count; D003214:Conditioning, Classical / Q000502:physiology*; D016572:Cyclosporine / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015213:Neuroimmunomodulation / Q000502:physiology*; D021641:Recognition, Psychology / Q000502:physiology; D012803:Sick Role; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013649:Taste / Q000276:immunology*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine