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In 1974 Robert Ader discovered that the immune system of rats can be conditioned to respond to external stimuli unrelated to immune function. Ader was investigating how long conditioned responses (in the sense of Pavlov's conditioning of dogs to drool when they heard a bell ring) might last in laboratory rats. To condition the rats, he used a combination of saccharine-laced water and the drug Cytoxan which induces nausea and suppresses the immune system. Ader was surprised to discover that after conditioning, just feeding the rats saccharine-laced water was sufficient to suppress the immune system of the rats. In other words, a signal via the nervous system (taste) was effecting immune function. This was one of the first scientific experiments that demonstrated that the nervous system can affect the immune system. Ader coined the phrase Psychoneuroimmunology and wrote the two-volume book Psychoneuroimmunology along with David L. Felten and Nicholas Cohen.
In 1981 David Felten, then working at the Indiana University of Medicine, discovered a network of nerves leading to blood vessels as well as cells of the immune system. The researchers also found nerves in the thymus and spleen terminating near clusters of lymphocytes, macrophages and mast cells, all of which help control immune function. This discovery provided one of the first indications of how neuro-immune interaction occurs.