Central infusion of interleukin-1 receptor antagonist blocks the reduction in social behavior produced by prior stressor exposure

Pro-inflammatory cytokines such as interleukin-1beta (IL-1β) in the brain modulate sickness behavior in rodents, in which animals show complex changes in behavior such as the reduction of general activity, reduced social motivation, and fever response. The present studies examined the impact of lipopolysacharide (LPS) and stressor (footshock) exposure on the later expression of social behavior in Sprague–Dawley rats using two separate behavioral paradigms. In Experiment 1, a traditional test for social interaction in which animals were allowed to investigate a juvenile rat in their home cages was conducted at 4 different time points following LPS or footshock treatment. In Experiment 2, social investigation task which allowed the animals to sniff the hole connected to the other chamber where a stimulus animal was placed, but prevented physical contact, was used to measure social investigation at several time points following LPS or footshock treatment. Both systemic infusion of LPS (100 µg/kg) and 2 h footshock exposure (80 shocks, 1 mA, 5 s duration) elicited a time-dependent reduction of social interaction (Experiment 1) and investigation (Experiment 2); LPS-treated rats displayed a more profound reduction of social investigation from 2 h to 6 h after treatment, while rats exposed to footshock showed a reduction 6 h after the footshock exposure. In Experiment 3, the footshock-induced reduction of social investigation was blocked by pretreatment with IL-1 receptor antagonist (IL-1Ra; 100 µg icv) infusion. Together, these findings support a growing body of literature showing that stress-dependent changes in brain cytokines play a key role in mediating behavioral consequences of stressor exposure.