Conditioning in the rat: an in vivo model to investigate the molecular mechanisms and clinical implications of brain–immune communication

A wealth of in vitro and ex vivo evidence has described both close anatomical interaction and functional bi-directional communication between the immune and central nervous systems (CNS). These data have provided a framework for understanding the physiological mechanisms whereby behavioural factors may impact immune-related disease. An understanding of this interaction, however, as well as verification of the biological relevance of communication among these systems, requires in vivo animal modelling. The development of psychoneuroimmunological models in the laboratory rat has played a key role in advancing the understanding of the influence of behaviour on immune status. One such paradigm is the behavioural conditioning of immune function in the rat. This elegant model is characterised by the ability to examine simultaneously both afferent and efferent brain-immune communication. Specifically, the role of peripheral cytokines in signalling the brain, as well as their anatomical and cellular targets in the CNS, can be identified. On the other hand, the neural and humoral pathways whereby the CNS influences the function and distribution of peripheral immunocytes can be demonstrated, together with the target hormone receptors on immunocompetent cells. Finally, the in vivo biological relevance of brain-immune communication is revealed by behavioural conditioning, demonstrating that clinically relevant conditions such as heart allograft survival can be modified by behavioural processes. Behavioural conditioning thereby provides an excellent example of the utility of in vivo laboratory rat models in psychoneuroimmunology research. Such paradigms not only provide a more complete knowledge of CNS-immune system interaction, but are the platform for determining potential clinical application of this information.