Immunity and emotions: lipopolysaccharide increases defensive behaviours and potentiates despair in mice

Many studies have pointed out the relationships between immunity and depression, supporting a neuroimmune hypothesis of depressive disorders. However, despite the growing interest for such a hypothesis and the amount of clinical and experimental data available, the precise nature of this relationship between immunity and depression remains unclear. The present study aimed to investigate further the link between depression and immunity in mice using the modified version of the forced-swimming test. Based on a two-session test, results from our first experiment showed that endotoxin enhanced active defensive behaviours in mice during the first exposure to water, but was associated with increased immobility (i.e., 'behavioural despair') in the subsequent session. In our second experiment, we showed that these effects were blocked by a chronic antidepressant treatment with imipramine. Finally, we suggest a link between immunity and depression, based on the behavioural context in which immune activation takes place. We hypothesize that immune activation, by enhancing reactivity to the negative features of a given situation, increases defensive motivation of subjects, but therefore makes them more vulnerable to the deleterious emotional consequences of failure in defensive strategies.