Febrile and sleep responses to an immune challenge are affected by trait aggressiveness in rats

Sleep is altered in response to an immune challenge: non-rapid eye movement (NREM) sleep is increased and fragmented, REM sleep is inhibited. Sleep and immune response are affected by stress: several stressors inhibit sleep and increase waking time; stress-induced cortisol secretion affects the immune response, with immunosuppressive effects. Different levels of trait aggressiveness are associated with specific patterns of neuroendocrine and autonomic stress responsiveness. Aim of this study was to test the hypothesis that trait aggressiveness, by affecting response to stressors, modifies sleep alterations induced by the activation of the immune response. To this aim, rats were selected on the basis of their latency time to attack a male intruder in the resident-intruder test. Animals were instrumented for chronic recordings of sleep-wake activity and injected, intraperitoneally, with an immune challenge (250 μg/kg lipopolysaccharide - LPS, a component of gram-negative bacterial cell wall). Here we report that high aggressive (HA) rats responded to an immune challenge with a 24-h long increase in cortical brain temperature. During the first 12 post-injection hours, HA rats also responded with a prolonged increase in NREM sleep amount, and a 5-h long and continuous inhibition of REM sleep. In HA rats, the LPS-induced increase in the amount of time spent in NREM sleep was due to an increase in the number of episodes of this sleep phase, without any change in the bout duration. The LPS-induced REM sleep inhibition observed in HA rats was due to a decrease in both the number and duration of REM sleep bouts. In HA rats, during REM sleep, LPS administration significantly reduced the power of the EEG theta band. In non-aggressive (NA) rats, in response to LPS administration, cortical brain temperature was increased only for two hours, NREM sleep was unaffected, and REM sleep inhibition was scattered along the first 8 post-injection hours. The LPS-induced changes in the number of NREM sleep bouts of NA rats were limited to few and scattered hours, with a change in bout duration only in a single hour. A combination of decreases, in few hours, in both REM sleep bouts and their duration contributed to the REM sleep inhibition observed in NA rats. In NA rats, the power of EEG theta band was not modified, during REM sleep, by LPS administration. Gross motor activity was inhibited in both HA and NA rats. Results of this study show that trait aggressiveness affects febrile and sleep responses to an immune challenge.